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Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (BEACON CRC)

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ClinicalTrials.gov Identifier: NCT02928224
Recruitment Status : Active, not recruiting
First Posted : October 10, 2016
Results First Posted : July 14, 2020
Last Update Posted : February 17, 2021
Sponsor:
Collaborators:
Merck KGaA, Darmstadt, Germany
Pierre Fabre Medicament
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition BRAF V600E-mutant Metastatic Colorectal Cancer
Interventions Drug: Encorafenib
Drug: Binimetinib
Drug: Cetuximab
Drug: Irinotecan
Drug: Folinic Acid
Drug: 5-Fluorouracil
Enrollment 702
Recruitment Details Patients were at least 18 years of age with confirmed metastatic colorectal cancer (CRC) whose disease had progressed after 1 or 2 prior regimens in the metastatic setting and whose tumor tissue was BRAF V600E-mutant as previously determined by a local assay at any time prior to Screening
Pre-assignment Details  
Arm/Group Title Combined Safety Lead-in Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Period Title: Overall Study
Started 37 224 220 221
Completed 0 0 0 0
Not Completed 37 224 220 221
Reason Not Completed
Randomized, Not Treated             0             2             4             28
Treatment Ongoing             6             78             78             37
Progressive Disease             23             104             101             103
Adverse Event             2             11             11             10
Changes in Patient's Condition             3             9             9             13
Death             1             7             5             11
Withdrawal by Subject             1             4             3             9
Dose Interruptions>28             1             2             2             4
Patient Decision to Discontinue Drug             0             2             2             4
Physician Decision             0             2             4             2
not listed             0             3             1             0
Arm/Group Title Combined Safety Lead-in (CSLI) Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm Total
Hide Arm/Group Description

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Total of all reporting groups
Overall Number of Baseline Participants 37 224 220 221 702
Hide Baseline Analysis Population Description
The baseline analysis population consists of the Full Analysis Set (FAS). For patients in the CSLI, the FAS includes all patients who received at least 1 dose of study drug and had at least 1 post treatment assessment, which may include death. For the randomized Phase 3 portion of the study, the FAS consists of all randomized patients.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
  62.2%
141
  62.9%
137
  62.3%
149
  67.4%
450
  64.1%
>=65 years
14
  37.8%
83
  37.1%
83
  37.7%
72
  32.6%
252
  35.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
58.3  (10.34) 59.5  (11.65) 60.2  (11.65) 58.4  (12.07) 59.3  (61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
Female
22
  59.5%
119
  53.1%
105
  47.7%
127
  57.5%
373
  53.1%
Male
15
  40.5%
105
  46.9%
115
  52.3%
94
  42.5%
329
  46.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
7
  18.9%
20
   8.9%
25
  11.4%
39
  17.6%
91
  13.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.7%
2
   0.9%
0
   0.0%
0
   0.0%
3
   0.4%
White
29
  78.4%
195
  87.1%
183
  83.2%
172
  77.8%
579
  82.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
7
   3.1%
12
   5.5%
10
   4.5%
29
   4.1%
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
North America
5
  13.5%
30
  13.4%
28
  12.7%
29
  13.1%
92
  13.1%
Europe
25
  67.6%
150
  67.0%
145
  65.9%
125
  56.6%
445
  63.4%
Rest of World (includes Mexico)
7
  18.9%
44
  19.6%
47
  21.4%
67
  30.3%
165
  23.5%
Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
0-Fully active
22
  59.5%
116
  51.8%
112
  50.9%
108
  48.9%
358
  51.0%
1-Restircted in physically strenuous activity
15
  40.5%
108
  48.2%
104
  47.3%
113
  51.1%
340
  48.4%
2-Ambulatory and capable of all self-care
0
   0.0%
0
   0.0%
4
   1.8%
0
   0.0%
4
   0.6%
[1]
Measure Description: ECOG PS was used to assess the physical health of patients, and ranges from 0 (most active) to 5 (dead). Frequency counts and percentages of patients in each score category were provided by treatment arm and assessment visit.
Primary Tumor Location  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
Left Colon
11
  29.7%
79
  35.3%
83
  37.7%
68
  30.8%
241
  34.3%
Right Colon
23
  62.2%
126
  56.3%
110
  50.0%
119
  53.8%
378
  53.8%
Left and Right Colon
0
   0.0%
8
   3.6%
11
   5.0%
22
  10.0%
41
   5.8%
Unknown
3
   8.1%
11
   4.9%
16
   7.3%
12
   5.4%
42
   6.0%
Primary Tumor Removed  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
Completely Resected
20
  54.1%
133
  59.4%
123
  55.9%
122
  55.2%
398
  56.7%
Partially Resected/Unresected
17
  45.9%
91
  40.6%
97
  44.1%
99
  44.8%
304
  43.3%
Number of Organs Involved  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
>=2
16
  43.2%
114
  50.9%
117
  53.2%
123
  55.7%
370
  52.7%
>=3
21
  56.8%
110
  49.1%
103
  46.8%
98
  44.3%
332
  47.3%
Sites of Metastases  
Measure Type: Number
Unit of measure:  Sites
Number Analyzed 37 participants 224 participants 220 participants 221 participants 702 participants
Liver 24 144 134 128 430
Lung 10 86 83 86 265
Lymph Node 17 86 82 88 273
NodePeritoneum/Omentum 17 77 97 93 284
1.Primary Outcome
Title (Safety Lead-in) Number of Participants With Dose-limiting Toxicities (DLTs)
Hide Description [Not Specified]
Time Frame Cycle 1 (up to 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The Dose-determining Set (DDS) consisted of all CSLI patients from the Safety Set who either completed a minimum exposure requirement (received ≥ 75% dose intensity of the planned dose for each binimetinib, encorafenib and cetuximab) and had sufficient safety evaluations or experienced a dose-limiting toxicity (DLT).
Arm/Group Title Combined Safety Lead-in (CSLI)
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
5
  13.5%
2.Primary Outcome
Title (Safety Lead-in) Number of Participants With Adverse Events (AEs)
Hide Description Refer to AE/SAE section for additional data that were measured and analyzed.
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Patients were analyzed according to treatment received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
37
 100.0%
3.Primary Outcome
Title (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Hide Description [Not Specified]
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Patients were analyzed according to treatment received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
26
  70.3%
4.Primary Outcome
Title (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 221
Median (95% Confidence Interval)
Unit of Measure: months
9.03
(8.02 to 11.43)
5.42
(4.76 to 6.57)
5.Primary Outcome
Title (Phase 3) Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 111 107
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
29
(18.2 to 35.3)
2
(.2 to 6.6)
6.Secondary Outcome
Title (Safety Lead-in) Response Rate (ORR) by Investigator
Hide Description [Not Specified]
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Lead-in (SLI) Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
52.8
(35.5 to 69.6)
7.Secondary Outcome
Title (Safety Lead-in) Response Rate (ORR) by BICR
Hide Description ORR per RECIST, v1.1, defined as the number of patients achieving an overall best response of CR or partial response (PR) divided by the total number of patients
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.7
(25.5 to 59.2)
8.Secondary Outcome
Title (Safety Lead-in) Duration of Response (DOR) by Investigator
Hide Description [Not Specified]
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
6.47
(4.17 to 11.07)
9.Secondary Outcome
Title (Safety Lead-in) Duration of Response (DOR) by BICR
Hide Description DOR defined as the time from first radiographic evidence of response to the earliest documented disease progression or death due to underlying disease
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
8.15 [1] 
(2.79 to NA)
[1]
NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.
10.Secondary Outcome
Title (Safety Lead-in) Time to Response by Investigator
Hide Description Time to response defined as the time from first dose to first radiographic evidence of response
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
1.45
(1.38 to 1.64)
11.Secondary Outcome
Title (Safety Lead-in) Time to Response by BICR
Hide Description Time to response defined as the time from first dose to first radiographic evidence of response
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
1.45
(1.38 to 1.64)
12.Secondary Outcome
Title (Safety Lead-in) Progression-free Survival (PFS) by Investigator
Hide Description [Not Specified]
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
8.08
(5.59 to 9.3)
13.Secondary Outcome
Title (Safety Lead-in) Progression-free Survival (PFS) by BICR
Hide Description PFS defined as the time from first dose to the earliest documented disease progression or death due to any cause
Time Frame Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: months
5.59
(4.44 to 9.3)
14.Secondary Outcome
Title (Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 220 221
Median (95% Confidence Interval)
Unit of Measure: months
8.41
(7.46 to 11.04)
5.42
(4.76 to 6.57)
15.Secondary Outcome
Title (Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3: Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 224 220
Median (95% Confidence Interval)
Unit of Measure: months
9.03
(8.02 to 11.43)
8.41
(7.46 to 11.04)
16.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 221
Median (95% Confidence Interval)
Unit of Measure: months
4.30
(4.14 to 5.19)
1.51
(1.45 to 1.71)
17.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 221
Median (95% Confidence Interval)
Unit of Measure: months
4.47
(4.24 to 5.36)
1.58
(1.51 to 2.07)
18.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 220 221
Median (95% Confidence Interval)
Unit of Measure: months
4.21
(3.71 to 5.36)
1.51
(1.45 to 1.71)
19.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 220 221
Median (95% Confidence Interval)
Unit of Measure: months
4.27
(4.04 to 5.36)
1.58
(1.51 to 2.07)
20.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3: Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 224 220
Median (95% Confidence Interval)
Unit of Measure: months
4.30
(4.14 to 5.19)
4.21
(3.71 to 5.36)
21.Secondary Outcome
Title (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3: Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 224 220
Median (95% Confidence Interval)
Unit of Measure: months
4.47
(4.24 to 5.36)
4.27
(4.04 to 5.36)
22.Secondary Outcome
Title Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 221
Measure Type: Count of Participants
Unit of Measure: Participants
49
  21.9%
7
   3.2%
23.Secondary Outcome
Title (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 113 107
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
23
(13.4 to 29)
2
(.2 to 6.6)
24.Secondary Outcome
Title (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 220 221
Measure Type: Count of Participants
Unit of Measure: Participants
31
  14.1%
7
   3.2%
25.Secondary Outcome
Title Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Triplet Arm Phase 3: Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 111 113
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
29
(18.2 to 35.3)
23
(13.4 to 29)
26.Secondary Outcome
Title Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Triplet Arm Phase 3: Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 224 220
Measure Type: Count of Participants
Unit of Measure: Participants
49
  21.9%
31
  14.1%
27.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 111 107
Median (95% Confidence Interval)
Unit of Measure: months
4.80
(2.96 to 9.69)
NA [1] 
(2.56 to NA)
[1]
NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.
28.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 111 107
Median (95% Confidence Interval)
Unit of Measure: months
4.80
(3.29 to 6.57)
5.75 [1] 
(2.56 to NA)
[1]
NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.
29.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 113 107
Median (95% Confidence Interval)
Unit of Measure: months
6.06
(4.07 to 8.28)
NA [1] 
(2.56 to NA)
[1]
NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.
30.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 113 107
Median (95% Confidence Interval)
Unit of Measure: months
5.70
(3.65 to 6.74)
5.75 [1] 
(2.56 to NA)
[1]
NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.
31.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 111 113
Median (95% Confidence Interval)
Unit of Measure: months
4.80
(2.96 to 9.69)
6.06
(4.07 to 8.28)
32.Secondary Outcome
Title (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 111 113
Median (95% Confidence Interval)
Unit of Measure: months
4.80
(3.29 to 6.57)
5.70
(3.65 to 6.74)
33.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 50 3
Median (95% Confidence Interval)
Unit of Measure: months
1.43
(1.41 to 1.51)
1.45
(1.41 to 2.63)
34.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 49 7
Median (95% Confidence Interval)
Unit of Measure: months
1.48
(1.41 to 1.51)
2.63
(1.45 to 2.79)
35.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 36 3
Median (95% Confidence Interval)
Unit of Measure: months
1.48
(1.41 to 1.58)
1.45
(1.41 to 2.63)
36.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 31 7
Median (95% Confidence Interval)
Unit of Measure: months
1.48
(1.41 to 1.54)
2.63
(1.45 to 2.79)
37.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 50 36
Median (95% Confidence Interval)
Unit of Measure: months
1.43
(1.41 to 1.51)
1.48
(1.41 to 1.58)
38.Secondary Outcome
Title (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator
Hide Description [Not Specified]
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 49 31
Median (95% Confidence Interval)
Unit of Measure: months
1.48
(1.41 to 1.51)
1.48
(1.41 to 1.54)
39.Secondary Outcome
Title (Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Hide Description The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 220 221
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 209 participants 201 participants 200 participants
62.8  (22.18) 60.7  (21.33) 62.8  (21.82)
Cycle 1 Day 1 Number Analyzed 138 participants 133 participants 120 participants
-2.4  (13.44) -4.3  (16.27) -3.4  (15.60)
Cycle 2 Day 1 Number Analyzed 181 participants 180 participants 123 participants
-1.6  (19.06) 3.8  (18.46) -1.9  (22.45)
Cycle 3 Day 1 Number Analyzed 148 participants 142 participants 51 participants
0.7  (18.86) 3.5  (19.96) -0.2  (24.07)
Cycle 4 Day 1 Number Analyzed 119 participants 105 participants 37 participants
0.2  (15.63) 4.2  (22.17) 1.4  (21.65)
Cycle 5 Day 1 Number Analyzed 99 participants 81 participants 26 participants
-1.1  (18.66) 4.3  (22.09) -2.2  (22.06)
Cycle 6 Day 1 Number Analyzed 68 participants 60 participants 13 participants
-4.0  (16.76) 5.6  (23.25) -4.5  (19.43)
Cycle 7 Day 1 Number Analyzed 47 participants 50 participants 10 participants
-2.5  (16.01) 4.3  (21.77) 1.7  (12.30)
Cycle 8 Day 1 Number Analyzed 39 participants 40 participants 7 participants
-2.6  (14.83) 4.2  (16.98) 0.0  (27.64)
Cycle 9 Day 1 Number Analyzed 33 participants 31 participants 7 participants
-5.8  (17.74) -5.6  (16.44) -4.8  (12.60)
Cycle 10 Day 1 Number Analyzed 23 participants 24 participants 4 participants
-3.3  (17.90) -2.8  (16.97) 2.1  (20.83)
Cycle 11 Day 1 Number Analyzed 16 participants 19 participants 1 participants
-5.2  (20.38) 3.9  (15.31) 33.3 [1]   (NA)
Cycle 12 Day 1 Number Analyzed 14 participants 18 participants 2 participants
0.0  (22.41) -4.6  (13.77) 4.2  (53.03)
Cycle 13 Day 1 Number Analyzed 9 participants 13 participants 1 participants
0.0  (20.41) -3.2  (14.25) 0.0 [2]   (NA)
Cycle 14 Day 1 Number Analyzed 7 participants 7 participants 0 participants
-1.2  (24.26) -6.0  (15.00)
Cycle 15 Day 1 Number Analyzed 7 participants 6 participants 0 participants
3.6  (33.63) 2.8  (8.61)
Cycle 16 Day 1 Number Analyzed 5 participants 3 participants 0 participants
-16.7  (42.08) -5.6  (9.62)
Cycle 17 Day 1 Number Analyzed 3 participants 3 participants 0 participants
-27.8  (20.97) -2.8  (12.73)
Cycle 18 Day 1 Number Analyzed 1 participants 3 participants 0 participants
-16.7 [2]   (NA) -8.3  (8.33)
Cycle 19 Day 1 Number Analyzed 1 participants 2 participants 0 participants
0.0 [2]   (NA) -8.3  (11.79)
Cycle 20 Day 1 Number Analyzed 1 participants 1 participants 0 participants
-25 [2]   (NA) -8 [2]   (NA)
Cycle 21 Day 1 Number Analyzed 1 participants 1 participants 0 participants
0.0 [2]   (NA) -16.7 [2]   (NA)
Cycle 22 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-16.7 [2]   (NA)
Cycle 23 Day 1 Number Analyzed 0 participants 1 participants 0 participants
0.0 [2]   (NA)
End of Treatment Number Analyzed 74 participants 72 participants 79 participants
-14.1  (22.66) -13.1  (21.61) -15.5  (27.04)
30 Day Follow Up Number Analyzed 24 participants 16 participants 21 participants
-17.4  (22.51) -10.4  (15.96) -24.6  (24.08)
[1]
Number analyzed is 1 so standard deviation (SD) is not available.
[2]
Number analyzed is 1 so SD is not available.
40.Secondary Outcome
Title (Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Hide Description FACT-C is a well-characterized and commonly used questionnaire that belongs to the Functional Assessment of Chronic Illness Therapy Measurement System (FACIT). The FACT-G (G for general) questionnaire (27 questions) constitutes the core of all subscales and is applicable to all tumor types. The FACT-C questionnaire contains 9 additional questions on symptoms specific to CRC, 2 of which are only answered by patients with ostomy appliances. These 9 CRC-specific questions are categorized as "additional concerns" on the questionnaire and constitute the "colorectal cancer subscale" score. The patient self-reports his/her QoL for the previous 7 days. The overall score is calculated across all items and a higher score reflects better quality of life (QoL). The table summarizes the functional well-being subscale, the individual questions are linearly scaled and combined to form the functional well-being subscale score, which ranges from 0-28 (higher is better QoL).
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 220 221
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 211 participants 199 participants 200 participants
16.3  (6.22) 16.2  (5.9) 16.8  (6.07)
Cycle 1 Day 1 Number Analyzed 142 participants 130 participants 117 participants
-0.2  (3.36) -0.9  (4.06) -1.4  (3.32)
Cycle 2 Day 1 Number Analyzed 183 participants 176 participants 123 participants
-0.3  (4.28) -0.6  (5.08) -0.9  (4.48)
Cycle 3 Day 1 Number Analyzed 148 participants 137 participants 50 participants
-0.2  (5.15) -0.2  (5.23) -0.7  (5.03)
Cycle 4 Day 1 Number Analyzed 119 participants 105 participants 37 participants
0.4  (4.53) -0.1  (4.66) -1.8  (6.48)
Cycle 5 Day 1 Number Analyzed 100 participants 81 participants 26 participants
0.7  (6.4) -0.2  (4.5) -1.6  (4.58)
Cycle 6 Day 1 Number Analyzed 68 participants 58 participants 13 participants
0.7  (6.05) 0.6  (4.56) -1.9  (5.3)
Cycle 7 Day 1 Number Analyzed 47 participants 49 participants 10 participants
0.5  (5.85) -0.1  (4.70) -0.5  (5.41)
Cycle 8 Day 1 Number Analyzed 40 participants 39 participants 8 participants
0.9  (6.35) 0.2  (4.24) -2.1  (4.97)
Cycle 9 Day 1 Number Analyzed 32 participants 30 participants 7 participants
-1.9  (4.32) -0.8  (3.74) -2.6  (2.30)
Cycle 10 Day 1 Number Analyzed 22 participants 24 participants 4 participants
-1.7  (4.76) -1.3  (3.59) 0.5  (4.36)
Cycle 11 Day 1 Number Analyzed 17 participants 19 participants 2 participants
-1.5  (4.47) -0.5  (4.65) -4.5  (7.78)
Cycle 12 Day 1 Number Analyzed 14 participants 18 participants 2 participants
-1.5  (4.93) -1.1  (4.61) -4.5  (9.19)
Cycle 13 Day 1 Number Analyzed 9 participants 13 participants 1 participants
-2.0  (6.76) -3.2  (5.34) -8.0 [1]   (NA)
Cycle 14 Day 1 Number Analyzed 7 participants 7 participants 0 participants
-2.4  (5.22) -4.0  (5.74)
Cycle 15 Day 1 Number Analyzed 7 participants 6 participants 0 participants
-2.3  (6.85) -1.5  (4.72)
Cycle 16 Day 1 Number Analyzed 5 participants 3 participants 0 participants
-4.2  (4.02) -0.7  (0.58)
Cycle 17 Day 1 Number Analyzed 3 participants 3 participants 0 participants
-6.7  (5.51) -0.7  (4.51)
Cycle 18 Day 1 Number Analyzed 1 participants 3 participants 0 participants
-5.0 [1]   (NA) -3.0  (4.36)
Cycle 19 Day 1 Number Analyzed 1 participants 2 participants 0 participants
-7.0 [1]   (NA) -6.0  (0.00)
Cycle 20 Day 1 Number Analyzed 1 participants 1 participants 0 participants
-6.0 [1]   (NA) -5.0 [1]   (NA)
Cycle 21 Day 1 Number Analyzed 1 participants 1 participants 0 participants
-9.0 -5.0
Cycle 22 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-12.0 [1]   (NA)
Cycle 23 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-9.0 [1]   (NA)
End of Treatment Number Analyzed 74 participants 73 participants 79 participants
-2.4  (4.84) -2.2  (5.14) -3.1  (6.06)
30 Day Follow Up Number Analyzed 24 participants 16 participants 21 participants
-3.5  (6.44) -0.8  (5.42) -4.2  (6.41)
[1]
Number analyzed is 1 so SD is not available.
41.Secondary Outcome
Title (Phase 3) Change From Baseline in the EuroQol-5D-5L (EQ-5D-5L) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Hide Description The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the patient and ranges from 0 to 100 (higher is better quality health).
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 220 221
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 210 participants 203 participants 199 participants
69.0  (19.03) 66.5  (19.51) 68.3  (19.71)
Cycle 1 Day 1 Number Analyzed 141 participants 135 participants 120 participants
0.8  (10.89) -0.9  (14.09) -2.1  (15.02)
Cycle 2 Day 1 Number Analyzed 183 participants 181 participants 124 participants
1.4  (14.74) 1.9  (14.81) -2.4  (17.20)
Cycle 3 Day 1 Number Analyzed 150 participants 141 participants 52 participants
3.0  (13.94) 4.2  (17.32) -1.4  (17.40)
Cycle 4 Day 1 Number Analyzed 118 participants 105 participants 37 participants
4.0  (13.06) 5.6  (14.87) -0.4  (15.14)
Cycle 5 Day 1 Number Analyzed 99 participants 80 participants 26 participants
3.3  (14.66) 5.1  (15.11) 2.5  (11.17)
Cycle 6 Day 1 Number Analyzed 66 participants 58 participants 13 participants
1.3  (13.33) 2.9  (16.84) -3.6  (13.26)
Cycle 7 Day 1 Number Analyzed 46 participants 47 participants 10 participants
1.4  (13.64) 3.6  (16.71) 2.4  (7.44)
Cycle 8 Day 1 Number Analyzed 39 participants 39 participants 8 participants
4.1  (10.77) 2.0  (16.11) -2.8  (12.95)
Cycle 9 Day 1 Number Analyzed 33 participants 30 participants 7 participants
0.3  (15.16) -4.0  (12.99) -8.1  (8.80)
Cycle 10 Day 1 Number Analyzed 23 participants 23 participants 4 participants
0.2  (13.34) -8.1  (13.68) -1.8  (2.36)
Cycle 11 Day 1 Number Analyzed 17 participants 18 participants 2 participants
0.2  (13.87) -0.1  (10.15) 4.0  (8.49)
Cycle 12 Day 1 Number Analyzed 13 participants 17 participants 2 participants
-4.0  (20.11) -0.6  (11.67) 1.5  (12.02)
Cycle 13 Day 1 Number Analyzed 9 participants 12 participants 1 participants
-3.0  (17.17) -4.1  (14.41) -2.0 [1]   (NA)
Cycle 14 Day 1 Number Analyzed 7 participants 7 participants 0 participants
-4.0  (18.06) -0.4  (13.99)
Cycle 15 Day 1 Number Analyzed 7 participants 6 participants 0 participants
-3.4  (14.67) 4.2  (7.36)
Cycle 16 Day 1 Number Analyzed 5 participants 3 participants 0 participants
-10.4  (24.87) 3.3  (2.89)
Cycle 17 Day 1 Number Analyzed 3 participants 3 participants 0 participants
-18.3  (20.21) 1.7  (5.77)
Cycle 18 Day 1 Number Analyzed 1 participants 3 participants 0 participants
7.0 [1]   (NA) -3.3  (2.89)
Cycle 19 Day 1 Number Analyzed 1 participants 2 participants 0 participants
8.0 [1]   (NA) -5.5  (13.44)
Cycle 20 Day 1 Number Analyzed 1 participants 1 participants 0 participants
8.0 [1]   (NA) 2.0 [1]   (NA)
Cycle 21 Day 1 Number Analyzed 1 participants 1 participants 0 participants
8.0 [1]   (NA) -5.0 [1]   (NA)
Cycle 22 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-5.0 [1]   (NA)
Cycle 23 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-5.0 [1]   (NA)
End of Treatment Number Analyzed 75 participants 72 participants 80 participants
-8.5  (17.40) -8.0  (18.99) -12.7  (21.34)
30 Day Follow Up Number Analyzed 24 participants 16 participants 21 participants
-11.1  (20.23) -5.9  (20.18) -11.0  (17.51)
[1]
Number analyzed is 1 so SD is not available.
42.Secondary Outcome
Title (Phase 3) Change From Baseline in the Patient Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Hide Description The PGIC is a measure of patients' perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other patient reported outcome (PROs). For this assessment, patients answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse."
Time Frame Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.
Arm/Group Title Phase 3: Triplet Arm Phase 3:Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

Overall Number of Participants Analyzed 224 220 221
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 153 participants 152 participants 149 participants
3.8  (1.30) 3.8  (1.30) 3.9  (1.28)
Cycle 1 Day 1 Number Analyzed 91 participants 92 participants 83 participants
-0.1  (0.93) 0.1  (1.21) 0.0  (0.90)
Cycle 2 Day 1 Number Analyzed 127 participants 130 participants 90 participants
-0.7  (1.44) -0.8  (1.60) -0.3  (1.52)
Cycle 3 Day 1 Number Analyzed 101 participants 105 participants 37 participants
-0.9  (1.44) -1.2  (1.53) -0.5  (1.56)
Cycle 4 Day 1 Number Analyzed 80 participants 79 participants 28 participants
-0.9  (1.49) -1.1  (1.68) -0.5  (1.35)
Cycle 5 Day 1 Number Analyzed 66 participants 59 participants 19 participants
-0.9  (1.61) -1.1  (1.69) -0.7  (1.41)
Cycle 6 Day 1 Number Analyzed 45 participants 40 participants 9 participants
-0.8  (1.31) -1.2  (1.70) -0.8  (1.39)
Cycle 7 Day 1 Number Analyzed 30 participants 36 participants 7 participants
-1.1  (1.44) -1.0  (1.61) -1.1  (1.07)
Cycle 8 Day 1 Number Analyzed 23 participants 27 participants 5 participants
-1.2  (1.56) -1.1  (1.58) -1.0  (0.71)
Cycle 9 Day 1 Number Analyzed 21 participants 21 participants 5 participants
-0.8  (1.26) -0.9  (1.37) -1.0  (0.71)
Cycle 10 Day 1 Number Analyzed 15 participants 17 participants 3 participants
-0.5  (1.51) -0.6  (1.28) -0.3  (0.58)
Cycle 11 Day 1 Number Analyzed 13 participants 13 participants 2 participants
-0.9  (1.38) -1.1  (1.38) 0.0  (0.00)
Cycle 12 Day 1 Number Analyzed 11 participants 12 participants 2 participants
-0.9  (1.45) -0.8  (1.36) -0.5  (0.71)
Cycle 13 Day 1 Number Analyzed 8 participants 10 participants 1 participants
-1.3  (1.39) -0.9  (1.52) -1.0 [1]   (NA)
Cycle 14 Day 1 Number Analyzed 7 participants 6 participants 0 participants
-1.1  (1.46) -1.5  (1.05)
Cycle 15 Day 1 Number Analyzed 6 participants 5 participants 0 participants
-1.2  (1.47) -1.6  (0.89)
Cycle 16 Day 1 Number Analyzed 4 participants 3 participants 0 participants
-2.0  (0.82) -0.7  (1.53)
Cycle 17 Day 1 Number Analyzed 3 participants 3 participants 0 participants
-1.3  (1.53) -1.0  (1.00)
Cycle 18 Day 1 Number Analyzed 1 participants 3 participants 0 participants
-2.0 [1]   (NA) -1.0  (1.00)
Cycle 19 Day 1 Number Analyzed 1 participants 2 participants 0 participants
-3.0 [1]   (NA) -0.5  (2.12)
Cycle 20 Day 1 Number Analyzed 1 participants 1 participants 0 participants
-3.0 [1]   (NA) -2.0 [1]   (NA)
Cycle 21 Day 1 Number Analyzed 1 participants 1 participants 0 participants
-3.0 [1]   (NA) -2.0 [1]   (NA)
Cycle 22 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-2.0 [1]   (NA)
Cycle 23 Day 1 Number Analyzed 0 participants 1 participants 0 participants
-2.0 [1]   (NA)
End of Treatment Number Analyzed 52 participants 54 participants 63 participants
0.3  (1.85) 0.1  (1.82) 0.4  (1.58)
30 Day Follow Up Number Analyzed 18 participants 10 participants 19 participants
-0.1  (2.08) 0.5  (1.43) 0.7  (1.34)
[1]
Number analyzed is 1 so SD is not available.
43.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Cetuximab
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetics (PK) set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*h
Cycle 1 Number Analyzed 34 participants
841000
(22.2%)
Cycle 2 Number Analyzed 32 participants
970000
(20.6%)
44.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Encorafenib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*h
Cycle 1 Number Analyzed 34 participants
11300
(61.5%)
Cycle 2 Number Analyzed 29 participants
6660
(61.7%)
45.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Binimetinib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*h
Cycle 1 Number Analyzed 35 participants
1960
(43.6%)
Cycle 2 Number Analyzed 26 participants
1540
(44.7%)
46.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Metabolite of Binimetinib (AR00426032)
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*h
Cycle 1 Number Analyzed 35 participants
206
(46.7%)
Cycle 2 Number Analyzed 26 participants
70.0
(95.5%)
47.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Number Analyzed 34 participants
195000
(22.2%)
Cycle 2 Number Analyzed 32 participants
199000
(26.8%)
48.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Number Analyzed 34 participants
3360
(65.1%)
Cycle 2 Number Analyzed 29 participants
2490
(75.6%)
49.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Number Analyzed 35 participants
654
(50.8%)
Cycle 2 Number Analyzed 26 participants
524
(70.1%)
50.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Number Analyzed 35 participants
59.9
(50.8%)
Cycle 2 Number Analyzed 26 participants
20.5
(119%)
51.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: hours
Cycle 1 Number Analyzed 34 participants
3.77
(1.83 to 6.05)
Cycle 2 Number Analyzed 32 participants
3.05
(1.00 to 6.17)
52.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: hours
Cycle 1 Number Analyzed 34 participants
2.00
(.883 to 6.25)
Cycle 2 Number Analyzed 29 participants
2.00
(.950 to 5.73)
53.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: hours
Cycle 1 Number Analyzed 35 participants
1.98
(.883 to 5.67)
Cycle 2 Number Analyzed 26 participants
1.04
(.900 to 4.00)
54.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Median (Full Range)
Unit of Measure: hours
Cycle 1 Number Analyzed 35 participants
2.00
(.833 to 5.78)
Cycle 2 Number Analyzed 26 participants
1.58
(.933 to 6.52)
55.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
55.3
(61.5%)
56.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
18.9
(191%)
57.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
55400
(54.8%)
58.Secondary Outcome
Title (Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Combined Safety Lead-in
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3.41
(68.5%)
59.Secondary Outcome
Title (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib
Hide Description The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set included all patients in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Phase 3: Triplet, Doublet and Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib + cetuximab.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Overall Number of Participants Analyzed 394
Geometric Mean (95% Confidence Interval)
Unit of Measure: L/h
16.4
(14.9 to 17.5)
60.Secondary Outcome
Title (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib
Hide Description The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set included all patients in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Phase 3: Triplet, Doublet and Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib + cetuximab.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Overall Number of Participants Analyzed 181
Geometric Mean (95% Confidence Interval)
Unit of Measure: L/h
19.0
(17.7 to 20.6)
61.Secondary Outcome
Title (Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab
Hide Description The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set included all patients in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Patients were analyzed according to the actual treatment and dose received.
Arm/Group Title Phase 3: Triplet, Doublet and Control Arm
Hide Arm/Group Description:

Encorafenib + binimetinib + cetuximab.

Encorafenib + cetuximab.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Overall Number of Participants Analyzed 261
Geometric Mean (95% Confidence Interval)
Unit of Measure: L/h
0.0154
(0.0114 to 0.0225)
Time Frame Adverse Events (AE) were collected during the study (duration of safety lead-in and phase 3,approximately 12 months (up to 28 days per cycle)), which began in 09Oct2016 and still ongoing.
Adverse Event Reporting Description An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
 
Arm/Group Title Combined Safety Lead-in Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm
Hide Arm/Group Description

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + binimetinib + cetuximab.

Encorafenib: Orally, once daily.

Binimetinib: Orally, twice daily.

Cetuximab: Standard of care.

Encorafenib + cetuximab.

Encorafenib: Orally, once daily.

Cetuximab: Standard of care.

Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.

Cetuximab: Standard of care.

Irinotecan: Standard of care.

Folinic Acid: Standard of care.

5-Fluorouracil: Standard of care.

All-Cause Mortality
Combined Safety Lead-in Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/37 (2.70%)   7/222 (3.15%)   5/216 (2.31%)   11/193 (5.70%) 
Hide Serious Adverse Events
Combined Safety Lead-in Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/37 (59.46%)   93/222 (41.89%)   71/216 (32.87%)   71/193 (36.79%) 
Blood and lymphatic system disorders         
Anaemia * 1  1/37 (2.70%)  4/222 (1.80%)  1/216 (0.46%)  1/193 (0.52%) 
Pulmonary embolism * 1  1/37 (2.70%)  8/222 (3.60%)  3/216 (1.39%)  4/193 (2.07%) 
Bacteraemia * 1  0/37 (0.00%)  3/222 (1.35%)  0/216 (0.00%)  1/193 (0.52%) 
Febrile neutropenia * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  5/193 (2.59%) 
Infusion-related reaction * 1  5/37 (13.51%)  1/222 (0.45%)  7/216 (3.24%)  6/193 (3.11%) 
Blood creatinine increased * 1  2/37 (5.41%)  2/222 (0.90%)  0/216 (0.00%)  0/193 (0.00%) 
Neutropenia * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Cardiac disorders         
Cardiac arrest * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Cardio-respiratory * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  1/193 (0.52%) 
Atrial fibrillation * 1  0/37 (0.00%)  0/222 (0.00%)  3/216 (1.39%)  0/193 (0.00%) 
Gastrointestinal disorders         
Diarrhoea * 1  1/37 (2.70%)  12/222 (5.41%)  1/216 (0.46%)  10/193 (5.18%) 
Vomiting * 1  2/37 (5.41%)  3/222 (1.35%)  2/216 (0.93%)  3/193 (1.55%) 
Gastrointestinal perforation * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Ileus * 1  0/37 (0.00%)  5/222 (2.25%)  3/216 (1.39%)  2/193 (1.04%) 
Intestinal obstruction * 1  0/37 (0.00%)  6/222 (2.70%)  14/216 (6.48%)  8/193 (4.15%) 
Large intestine perforation * 1  1/37 (2.70%)  3/222 (1.35%)  2/216 (0.93%)  2/193 (1.04%) 
Gastrointestinal haemorrhage * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  0/193 (0.00%) 
Subileus * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Abdominal pain * 1  0/37 (0.00%)  4/222 (1.80%)  3/216 (1.39%)  4/193 (2.07%) 
Bile duct obstruction * 1  0/37 (0.00%)  2/222 (0.90%)  3/216 (1.39%)  2/193 (1.04%) 
Large intestinal obstruction * 1  0/37 (0.00%)  1/222 (0.45%)  3/216 (1.39%)  0/193 (0.00%) 
Subileus * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  3/193 (1.55%) 
Small intestinal obstruction * 1  0/37 (0.00%)  2/222 (0.90%)  0/216 (0.00%)  6/193 (3.11%) 
Colitis * 1  1/37 (2.70%)  2/222 (0.90%)  0/216 (0.00%)  0/193 (0.00%) 
Abdominal distention * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Constipation * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  1/193 (0.52%) 
Duodenal obstruction * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Dyspepsia * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Gastritis * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Gastrointtestinal perforation * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Haematemesis * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
intestinal perforation * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Melaena * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  0/193 (0.00%) 
Pancreatitis * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  0/193 (0.00%) 
Pancreatitis acute * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Pancreatitis relapsing * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Rectal stenosis * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Rectal ulcer * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Abdominal hernia * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Anal haemorrhage * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  0/193 (0.00%) 
Ascites * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  1/193 (0.52%) 
Enterocolitis * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  1/193 (0.52%) 
Impaired gastric emptying * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  0/193 (0.00%) 
Large intestine ulcer * 1  1/37 (2.70%)  0/222 (0.00%)  0/216 (0.00%)  0/193 (0.00%) 
Proctalgia * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
General disorders         
Death * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Pain * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  2/193 (1.04%) 
Asthenia * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  1/193 (0.52%) 
Hepatobiliary disorders         
Hepatic failure * 1  0/37 (0.00%)  9/222 (4.05%)  0/216 (0.00%)  0/193 (0.00%) 
Jaundice * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  1/193 (0.52%) 
Immune system disorders         
Anaphylactic reaction * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Infections and infestations         
Peritonitis * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Respiratory tract infection * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Sepsis * 1  0/37 (0.00%)  6/222 (2.70%)  2/216 (0.93%)  0/193 (0.00%) 
Abdominal wall abscess * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Biliary tract infection * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  0/193 (0.00%) 
Cholangitis infective * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Endocarditis * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Erysipelas * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Gastrintestinal infection * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Urosepsis * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  0/193 (0.00%) 
Wound abscess * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Abdominal abscess * 1  1/37 (2.70%)  0/222 (0.00%)  1/216 (0.46%)  0/193 (0.00%) 
Abscess limb * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Anal abscess * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Bacteria sepsis * 1  1/37 (2.70%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Campylobacter gastroenteritis * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Metabolism and nutrition disorders         
Nausea * 1  1/37 (2.70%)  12/222 (5.41%)  3/216 (1.39%)  1/193 (0.52%) 
General physical health deterioration * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  2/193 (1.04%) 
Asthenia * 1  0/37 (0.00%)  4/222 (1.80%)  0/216 (0.00%)  0/193 (0.00%) 
Fatigue * 1  1/37 (2.70%)  2/222 (0.90%)  0/216 (0.00%)  0/193 (0.00%) 
Dehydration * 1  1/37 (2.70%)  2/222 (0.90%)  1/216 (0.46%)  1/193 (0.52%) 
Decreased appetite * 1  1/37 (2.70%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Colorectal cancer metastatic * 1  0/37 (0.00%)  2/222 (0.90%)  0/216 (0.00%)  0/193 (0.00%) 
Malignant neoplasm progression * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Neoplasm progression * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  1/193 (0.52%) 
Colon cancer * 1  1/37 (2.70%)  0/222 (0.00%)  2/216 (0.93%)  0/193 (0.00%) 
Colon cancer metastatic * 1  0/37 (0.00%)  0/222 (0.00%)  2/216 (0.93%)  1/193 (0.52%) 
Colorectal cancer * 1  0/37 (0.00%)  0/222 (0.00%)  1/216 (0.46%)  1/193 (0.52%) 
Cancer pain * 1  0/37 (0.00%)  1/222 (0.45%)  5/216 (2.31%)  1/193 (0.52%) 
Nervous system disorders         
Pyrexia * 1  2/37 (5.41%)  4/222 (1.80%)  1/216 (0.46%)  0/193 (0.00%) 
Cerebral ischaemia * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Epilepsy * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Psychiatric disorders         
Anxiety * 1  0/37 (0.00%)  2/222 (0.90%)  0/216 (0.00%)  0/193 (0.00%) 
Renal and urinary disorders         
Acute kidney injury * 1  0/37 (0.00%)  7/222 (3.15%)  4/216 (1.85%)  1/193 (0.52%) 
Urinary tract infection * 1  4/37 (10.81%)  2/222 (0.90%)  5/216 (2.31%)  1/193 (0.52%) 
Haematuria * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Hydronephrosis * 1  1/37 (2.70%)  1/222 (0.45%)  0/216 (0.00%)  1/193 (0.52%) 
Nephritis * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Renal failure * 1  2/37 (5.41%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Urinary retention * 1  0/37 (0.00%)  1/222 (0.45%)  0/216 (0.00%)  0/193 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Aspiration * 1  0/37 (0.00%)  0/222 (0.00%)  2/216 (0.93%)  0/193 (0.00%) 
Respiratory distress * 1  0/37 (0.00%)  0/222 (0.00%)  0/216 (0.00%)  1/193 (0.52%) 
Respiratory failure * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  3/193 (1.55%) 
1
Term from vocabulary, MedDRA (21.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combined Safety Lead-in Phase 3: Triplet Arm Phase 3: Doublet Arm Phase 3:Control Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/37 (100.00%)   217/222 (97.75%)   212/216 (98.15%)   188/193 (97.41%) 
Blood and lymphatic system disorders         
Anaemia * 1  16/37 (43.24%)  80/222 (36.04%)  35/216 (16.20%)  37/193 (19.17%) 
Hypomagnesaemia * 1  6/37 (16.22%)  20/222 (9.01%)  22/216 (10.19%)  17/193 (8.81%) 
Hypokalaemia * 1  3/37 (8.11%)  15/222 (6.76%)  13/216 (6.02%)  27/193 (13.99%) 
Neutropenia * 1  1/37 (2.70%)  3/222 (1.35%)  1/216 (0.46%)  36/193 (18.65%) 
Neutrophil count decreased * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  21/193 (10.88%) 
Cardiac disorders         
Palpitations * 1  2/37 (5.41%)  3/222 (1.35%)  3/216 (1.39%)  1/193 (0.52%) 
Eye disorders         
Vision blurred * 1  12/37 (32.43%)  25/222 (11.26%)  8/216 (3.70%)  1/193 (0.52%) 
Dry eye * 1  4/37 (10.81%)  6/222 (2.70%)  7/216 (3.24%)  2/193 (1.04%) 
Retinal detachment * 1  2/37 (5.41%)  6/222 (2.70%)  1/216 (0.46%)  0/193 (0.00%) 
Gastrointestinal disorders         
Diarrhoea * 1  28/37 (75.68%)  137/222 (61.71%)  72/216 (33.33%)  93/193 (48.19%) 
Nausea * 1  22/37 (59.46%)  100/222 (45.05%)  74/216 (34.26%)  80/193 (41.45%) 
Vomiting * 1  18/37 (48.65%)  85/222 (38.29%)  46/216 (21.30%)  56/193 (29.02%) 
Abdominal pain * 1  14/37 (37.84%)  65/222 (29.28%)  49/216 (22.69%)  48/193 (24.87%) 
Decreased appetite * 1  14/37 (37.84%)  63/222 (28.38%)  68/216 (31.48%)  52/193 (26.94%) 
Constipation * 1  14/37 (37.84%)  55/222 (24.77%)  33/216 (15.28%)  35/193 (18.13%) 
Abdominal pain upper * 1  4/37 (10.81%)  20/222 (9.01%)  19/216 (8.80%)  15/193 (7.77%) 
Dyspepsia * 1  4/37 (10.81%)  16/222 (7.21%)  7/216 (3.24%)  7/193 (3.63%) 
Flatulence * 1  0/37 (0.00%)  13/222 (5.86%)  6/216 (2.78%)  3/193 (1.55%) 
Rectal haemorrhage * 1  3/37 (8.11%)  12/222 (5.41%)  5/216 (2.31%)  1/193 (0.52%) 
Dry Mouth * 1  2/37 (5.41%)  11/222 (4.95%)  8/216 (3.70%)  7/193 (3.63%) 
Gastroesophageal reflux disease * 1  2/37 (5.41%)  11/222 (4.95%)  4/216 (1.85%)  5/193 (2.59%) 
Abdominal distension * 1  2/37 (5.41%)  9/222 (4.05%)  12/216 (5.56%)  8/193 (4.15%) 
Intestinal obstruction * 1  0/37 (0.00%)  8/222 (3.60%)  12/216 (5.56%)  8/193 (4.15%) 
General disorders         
Chills * 1  4/37 (10.81%)  13/222 (5.86%)  6/216 (2.78%)  3/193 (1.55%) 
Malaise * 1  6/37 (16.22%)  6/222 (2.70%)  5/216 (2.31%)  11/193 (5.70%) 
Infections and infestations         
Pyrexia * 1  15/37 (40.54%)  45/222 (20.27%)  35/216 (16.20%)  27/193 (13.99%) 
Urinary tract infection * 1  7/37 (18.92%)  18/222 (8.11%)  16/216 (7.41%)  6/193 (3.11%) 
Paronychia * 1  6/37 (16.22%)  17/222 (7.66%)  8/216 (3.70%)  17/193 (8.81%) 
Rash pustular * 1  5/37 (13.51%)  13/222 (5.86%)  4/216 (1.85%)  4/193 (2.07%) 
Conjunctivitis * 1  2/37 (5.41%)  10/222 (4.50%)  8/216 (3.70%)  2/193 (1.04%) 
Cystitis * 1  2/37 (5.41%)  6/222 (2.70%)  1/216 (0.46%)  1/193 (0.52%) 
Injury, poisoning and procedural complications         
Infusion related reaction * 1  3/37 (8.11%)  5/222 (2.25%)  20/216 (9.26%)  13/193 (6.74%) 
Investigations         
Blood creatine phosphokinase increased * 1  13/37 (35.14%)  20/222 (9.01%)  1/216 (0.46%)  3/193 (1.55%) 
Blood creatine increased * 1  11/37 (29.73%)  18/222 (8.11%)  4/216 (1.85%)  1/193 (0.52%) 
Alanine aminotransferase increased * 1  6/37 (16.22%)  15/222 (6.76%)  12/216 (5.56%)  12/193 (6.22%) 
Aspartate aminotransferase increased * 1  7/37 (18.92%)  13/222 (5.86%)  8/216 (3.70%)  13/193 (6.74%) 
Ejection fraction decreased * 1  5/37 (13.51%)  8/222 (3.60%)  0/216 (0.00%)  0/193 (0.00%) 
Blood bilirubin increased * 1  3/37 (8.11%)  6/222 (2.70%)  10/216 (4.63%)  8/193 (4.15%) 
White blood cell count decrease * 1  0/37 (0.00%)  1/222 (0.45%)  1/216 (0.46%)  14/193 (7.25%) 
Metabolism and nutrition disorders         
Fatigue * 1  20/37 (54.05%)  73/222 (32.88%)  65/216 (30.09%)  53/193 (27.46%) 
Asthenia * 1  6/37 (16.22%)  55/222 (24.77%)  46/216 (21.30%)  49/193 (25.39%) 
Weight decreased * 1  3/37 (8.11%)  24/222 (10.81%)  21/216 (9.72%)  11/193 (5.70%) 
Hypomagnesaemia * 1  6/37 (16.22%)  20/222 (9.01%)  22/216 (10.19%)  17/193 (8.81%) 
Hypoalbuminaemia * 1  4/37 (10.81%)  16/222 (7.21%)  5/216 (2.31%)  5/193 (2.59%) 
Hyperglycaemia * 1  1/37 (2.70%)  10/222 (4.50%)  7/216 (3.24%)  5/193 (2.59%) 
Dehydration * 1  2/37 (5.41%)  9/222 (4.05%)  4/216 (1.85%)  8/193 (4.15%) 
Musculoskeletal and connective tissue disorders         
PPE syndrome * 1  6/37 (16.22%)  28/222 (12.61%)  9/216 (4.17%)  14/193 (7.25%) 
Back Pain * 1  8/37 (21.62%)  25/222 (11.26%)  22/216 (10.19%)  23/193 (11.92%) 
Oedema peripheral * 1  6/37 (16.22%)  24/222 (10.81%)  18/216 (8.33%)  13/193 (6.74%) 
Arthralgia * 1  9/37 (24.32%)  23/222 (10.36%)  41/216 (18.98%)  1/193 (0.52%) 
Myalgia * 1  7/37 (18.92%)  18/222 (8.11%)  29/216 (13.43%)  4/193 (2.07%) 
Pain in extremity * 1  3/37 (8.11%)  15/222 (6.76%)  22/216 (10.19%)  1/193 (0.52%) 
Musculoskeletal pain * 1  2/37 (5.41%)  6/222 (2.70%)  27/216 (12.50%)  3/193 (1.55%) 
Muscle spasms * 1  2/37 (5.41%)  17/222 (7.66%)  3/216 (1.39%)  4/193 (2.07%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour Pain * 1  4/37 (10.81%)  3/222 (1.35%)  0/216 (0.00%)  2/193 (1.04%) 
Nervous system disorders         
Headache * 1  6/37 (16.22%)  16/222 (7.21%)  42/216 (19.44%)  5/193 (2.59%) 
Insomnia * 1  2/37 (5.41%)  11/222 (4.95%)  24/216 (11.11%)  11/193 (5.70%) 
Dizziness * 1  8/37 (21.62%)  13/222 (5.86%)  14/216 (6.48%)  15/193 (7.77%) 
Neuropathy peripheral * 1  1/37 (2.70%)  13/222 (5.86%)  8/216 (3.70%)  5/193 (2.59%) 
Dysgeusia * 1  6/37 (16.22%)  11/222 (4.95%)  9/216 (4.17%)  7/193 (3.63%) 
Peripheral sensory neuropathy * 1  6/37 (16.22%)  8/222 (3.60%)  4/216 (1.85%)  4/193 (2.07%) 
Syncope * 1  2/37 (5.41%)  3/222 (1.35%)  2/216 (0.93%)  0/193 (0.00%) 
Psychiatric disorders         
Insomnia * 1  2/37 (5.41%)  11/222 (4.95%)  24/216 (11.11%)  11/193 (5.70%) 
Depression * 1  2/37 (5.41%)  4/222 (1.80%)  4/216 (1.85%)  1/193 (0.52%) 
Renal and urinary disorders         
Acute kidney injury * 1  1/37 (2.70%)  11/222 (4.95%)  4/216 (1.85%)  1/193 (0.52%) 
Haematuria * 1  2/37 (5.41%)  10/222 (4.50%)  4/216 (1.85%)  4/193 (2.07%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  5/37 (13.51%)  23/222 (10.36%)  16/216 (7.41%)  10/193 (5.18%) 
Dyspnoea * 1  12/37 (32.43%)  17/222 (7.66%)  23/216 (10.65%)  17/193 (8.81%) 
Pulmonary embolism * 1  2/37 (5.41%)  10/222 (4.50%)  3/216 (1.39%)  8/193 (4.15%) 
Epistaxis * 1  1/37 (2.70%)  7/222 (3.15%)  15/216 (6.94%)  7/193 (3.63%) 
Dysphonia * 1  1/37 (2.70%)  5/222 (2.25%)  11/216 (5.09%)  3/193 (1.55%) 
Rhinnorrhoea * 1  3/37 (8.11%)  5/222 (2.25%)  5/216 (2.31%)  1/193 (0.52%) 
Skin and subcutaneous tissue disorders         
Dermatitis acneiform * 1  25/37 (67.57%)  108/222 (48.65%)  63/216 (29.17%)  76/193 (39.38%) 
Dry Skin * 1  19/37 (51.35%)  46/222 (20.72%)  24/216 (11.11%)  13/193 (6.74%) 
Rash * 1  3/37 (8.11%)  42/222 (18.92%)  25/216 (11.57%)  27/193 (13.99%) 
Stomatitis * 1  6/37 (16.22%)  31/222 (13.96%)  12/216 (5.56%)  44/193 (22.80%) 
Pruritus * 1  3/37 (8.11%)  28/222 (12.61%)  20/216 (9.26%)  9/193 (4.66%) 
Melanocytic naevus * 1  1/37 (2.70%)  1/222 (0.45%)  31/216 (14.35%)  0/193 (0.00%) 
Palmar-planar erythrodysaesthesia * 1  6/37 (16.22%)  28/222 (12.61%)  9/216 (4.17%)  14/193 (7.25%) 
Rash maculo-papular * 1  5/37 (13.51%)  18/222 (8.11%)  17/216 (7.87%)  11/193 (5.70%) 
Skin fissures * 1  9/37 (24.32%)  15/222 (6.76%)  5/216 (2.31%)  10/193 (5.18%) 
Erythema * 1  2/37 (5.41%)  7/222 (3.15%)  10/216 (4.63%)  4/193 (2.07%) 
Eczema * 1  2/37 (5.41%)  5/222 (2.25%)  1/216 (0.46%)  1/193 (0.52%) 
Skin hyperpigmentation * 1  2/37 (5.41%)  1/222 (0.45%)  16/216 (7.41%)  2/193 (1.04%) 
Skin lesion * 1  0/37 (0.00%)  1/222 (0.45%)  17/216 (7.87%)  1/193 (0.52%) 
Vascular disorders         
Hypotension * 1  3/37 (8.11%)  7/222 (3.15%)  9/216 (4.17%)  3/193 (1.55%) 
Hypertension * 1  4/37 (10.81%)  6/222 (2.70%)  7/216 (3.24%)  6/193 (3.11%) 
1
Term from vocabulary, MedDRA (21.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in the clinical trials.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Pfizer
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02928224    
Other Study ID Numbers: ARRAY-818-302
BEACON CRC ( Other Identifier: Alias Study Number )
2015-005805-35 ( EudraCT Number )
C4221009 ( Other Identifier: Pfizer )
First Submitted: August 16, 2016
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