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A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (HER2CLIMB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02614794
Recruitment Status : Completed
First Posted : November 25, 2015
Results First Posted : September 28, 2020
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition HER2 Positive Breast Cancer
Interventions Drug: tucatinib
Drug: capecitabine
Drug: trastuzumab
Drug: placebo
Enrollment 612
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description Tucatinib in combination with capecitabine & trastuzumab Placebo in combination with capecitabine & trastuzumab
Period Title: Overall Study
Started 410 202
Completed 0 0
Not Completed 410 202
Reason Not Completed
On treatment             118             27
In long term follow up             148             85
Death             126             84
Withdrawal by Subject             16             5
Lost to Follow-up             2             0
Physician Decision             0             1
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra Total
Hide Arm/Group Description Tucatinib in combination with capecitabine & trastuzumab Placebo in combination with capecitabine & trastuzumab Total of all reporting groups
Overall Number of Baseline Participants 410 202 612
Hide Baseline Analysis Population Description
Intent-to-treat Overall Survival (ITT-OS) Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 202 participants 612 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
328
  80.0%
168
  83.2%
496
  81.0%
>=65 years
82
  20.0%
34
  16.8%
116
  19.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 410 participants 202 participants 612 participants
55
(22 to 80)
54
(25 to 82)
54
(22 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 202 participants 612 participants
Female
407
  99.3%
200
  99.0%
607
  99.2%
Male
3
   0.7%
2
   1.0%
5
   0.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 202 participants 612 participants
Hispanic or Latino
37
   9.0%
14
   6.9%
51
   8.3%
Not Hispanic or Latino
362
  88.3%
184
  91.1%
546
  89.2%
Unknown or Not Reported
11
   2.7%
4
   2.0%
15
   2.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 202 participants 612 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
18
   4.4%
5
   2.5%
23
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
41
  10.0%
14
   6.9%
55
   9.0%
White
287
  70.0%
157
  77.7%
444
  72.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
64
  15.6%
26
  12.9%
90
  14.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 410 participants 202 participants 612 participants
United States
220
  53.7%
111
  55.0%
331
  54.1%
France
29
   7.1%
17
   8.4%
46
   7.5%
United Kingdom
33
   8.0%
12
   5.9%
45
   7.4%
Australia
27
   6.6%
12
   5.9%
39
   6.4%
Canada
26
   6.3%
12
   5.9%
38
   6.2%
Spain
19
   4.6%
7
   3.5%
26
   4.2%
Denmark
13
   3.2%
7
   3.5%
20
   3.3%
Germany
9
   2.2%
8
   4.0%
17
   2.8%
Israel
13
   3.2%
3
   1.5%
16
   2.6%
Belgium
4
   1.0%
6
   3.0%
10
   1.6%
Italy
6
   1.5%
3
   1.5%
9
   1.5%
Austria
6
   1.5%
1
   0.5%
7
   1.1%
Portugal
3
   0.7%
1
   0.5%
4
   0.7%
Czech Republic
2
   0.5%
1
   0.5%
3
   0.5%
Switzerland
0
   0.0%
1
   0.5%
1
   0.2%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 202 participants 612 participants
0: Normal activity
204
  49.8%
94
  46.5%
298
  48.7%
1: Symptoms, but ambulatory
206
  50.2%
108
  53.5%
314
  51.3%
[1]
Measure Description: 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed <50% of the time; 3= In bed >50% of the time; 4=100% bedridden; 5=Dead
1.Primary Outcome
Title Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)
Hide Description Defined as the time from the date of randomization to the date of documented disease progression.
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat Progression Free Survival (ITT-PFS) Population: Includes the first 480 randomized participants in the ITT analysis population (evaluated by their random treatment assignment).
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 320 160
Median (Inter-Quartile Range)
Unit of Measure: months
7.8
(4.3 to 17.8)
5.6
(3.0 to 9.7)
2.Secondary Outcome
Title PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR
Hide Description Defined as the time from the date of randomization to the date of documented disease progression.
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-PFSBrainMets population: included all randomized subjects with brain metastases (evaluated by their random treatment assignment).
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 198 93
Median (Inter-Quartile Range)
Unit of Measure: months
7.6
(4.2 to 11.8)
5.4
(3.0 to 7.5)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as time from randomization to death from any cause
Time Frame 35.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 410 202
Median (95% Confidence Interval)
Unit of Measure: months
21.9
(18.3 to 31.0)
17.4
(13.6 to 19.9)
4.Secondary Outcome
Title Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR
Hide Description Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT - PFS population, subset of participants with measurable disease by BICR at baseline. The ITT-PFS Population includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 273 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.7
(34.8 to 46.7)
23.4
(16.6 to 31.3)
5.Secondary Outcome
Title ORR Per RECIST 1.1 as Determined by Investigator Assessment
Hide Description Defined as achieving a best overall response of confirmed CR or confirmed PR.
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT - PFS population, subset of participants with measurable disease by investigator at baseline. The ITT-PFS Population includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 280 139
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.4
(35.6 to 47.4)
23.0
(16.3 to 30.9)
6.Secondary Outcome
Title PFS Per RECIST 1.1 as Determined by Investigator Assessment
Hide Description Defined as the time from the date of randomization to the date of documented disease progression
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-PFS Population: Includes the first 480 randomized participants in the ITT analysis population (evaluated by their randomized treatment assignment).
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 320 160
Median (Inter-Quartile Range)
Unit of Measure: months
7.5
(4.1 to 13.1)
4.3
(2.7 to 8.4)
7.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR
Hide Description Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Time Frame 24.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 410 202
Median (Inter-Quartile Range)
Unit of Measure: months
8.3
(4.3 to 12.8)
6.3
(4.2 to 9.0)
8.Secondary Outcome
Title DOR Per RECIST 1.1 as Determined by Investigator Assessment
Hide Description Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Time Frame 33.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 410 202
Median (Inter-Quartile Range)
Unit of Measure: months
7.0
(4.3 to 12.9)
6.9
(4.1 to 9.6)
9.Secondary Outcome
Title Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1
Hide Description Clinical benefit was defined as achieving stable disease (SD) or non-complete response (CR)/non-progressive disease (PD) for at least 6 months or a best overall response of confirmed CR or confirmed partial response (PR).
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 410 202
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
59.8
(54.8 to 64.5)
38.1
(31.4 to 45.2)
10.Secondary Outcome
Title CBR Per RECIST 1.1 as Determined by Investigator Assessment
Hide Description Clinical benefit was defined as achieving stable disease (SD) or non-CR/non-PD for at least 6 months or a best overall response of confirmed CR or confirmed PR.
Time Frame 34.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-OS Population: Includes all randomized participants evaluated by their randomized treatment assignment.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 410 202
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.0
(53.1 to 62.9)
37.6
(30.9 to 44.7)
11.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Time Frame 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 404 197
Measure Type: Count of Participants
Unit of Measure: Participants
Any treatment-emergent AE (TEAE)
401
  99.3%
191
  97.0%
Any Grade 3 or higher TEAE
223
  55.2%
96
  48.7%
Any treatment-emergent serious AE
104
  25.7%
53
  26.9%
TEAE leading to death
8
   2.0%
6
   3.0%
12.Secondary Outcome
Title Frequency of Dose Modifications
Hide Description [Not Specified]
Time Frame 35.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 404 197
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs resulting in tuc/pbo dose modification
220
  54.5%
81
  41.1%
TEAEs resulting in tucatinib/placebo dose hold
216
  53.5%
80
  40.6%
TEAEs resulting in tuc/pbo dose reduction
84
  20.8%
21
  10.7%
TEAEs resulting capecitabine dose modification
313
  77.5%
122
  61.9%
TEAEs resulting in capecitabine dose hold
276
  68.3%
113
  57.4%
TEAEs resulting in capecitabine dose reduction
243
  60.1%
77
  39.1%
TEAEs resulting trastuzumab dose modification
104
  25.7%
38
  19.3%
TEAEs resulting in trastuzumab dose hold
104
  25.7%
38
  19.3%
13.Secondary Outcome
Title Incidence of Health Resources Utilization
Hide Description Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.
Time Frame 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Population: Includes all randomized participants who received at least one dose of study treatment (tucatinib/placebo, trastuzumab, or capecitabine), with participants allocated to the treatment group associated with the regimen actually received.
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 404 197
Measure Type: Number
Unit of Measure: hospitalizations
Total number of hospitalizations 143 75
Hospitalization for AE 124 64
Planned hospitalization (other than AE) 10 6
Ambulatory Surgery 3 0
Other 6 5
14.Secondary Outcome
Title Pharmacokinetic Measure: Ctrough of Tucatinib
Hide Description Individual plasma tucatinib concentrations at each sampling time
Time Frame 3.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) Analysis Set: Includes all randomized participants who received at least one dose of tucatinib and who had at least one evaluable PK assessment. Participants were evaluated by the treatment actually received.
Arm/Group Title Tuc+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 373
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 2, Day 1 (Pre-dose) 246.1  (260.9)
Cycle 3, Day 1 (Pre-dose) 227.6  (210.8)
Cycle 3, Day 1 (Post-dose) 507.1  (357.1)
Cycle 4, Day 1 (Pre-dose) 253.2  (236.1)
Cycle 5, Day 1 (Pre-dose) 257.6  (286.9)
Cycle 6, Day 1 (Pre-dose) 247.8  (225.1)
15.Secondary Outcome
Title Pharmacokinetic Measure: ONT-993
Hide Description Individual plasma primary metabolite concentrations at each sampling time
Time Frame 3.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: Includes all randomized participants who received at least one dose of tucatinib and who had at least one evaluable PK assessment. Participants were evaluated by the treatment actually received.
Arm/Group Title Tuc+Cap+Tra
Hide Arm/Group Description:
Tucatinib in combination with capecitabine & trastuzumab
Overall Number of Participants Analyzed 373
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 2, Day 1 (Pre-dose) 25.5  (24.4)
Cycle 3, Day 1 (Pre-dose) 22.6  (20.6)
Cycle 3, Day 1 (Post-dose) 47.7  (47.2)
Cycle 4, Day 1 (Pre-dose) 25.2  (24.3)
Cycle 5, Day 1 (Pre-dose) 24.5  (30.6)
Cycle 6, Day 1 (Pre-dose) 20.9  (18.0)
Time Frame 36.1 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tuc+Cap+Tra Pbo+Cap+Tra
Hide Arm/Group Description Tucatinib in combination with capecitabine & trastuzumab Placebo in combination with capecitabine & trastuzumab
All-Cause Mortality
Tuc+Cap+Tra Pbo+Cap+Tra
Affected / at Risk (%) Affected / at Risk (%)
Total   130/410 (31.71%)   85/202 (42.08%) 
Hide Serious Adverse Events
Tuc+Cap+Tra Pbo+Cap+Tra
Affected / at Risk (%) Affected / at Risk (%)
Total   104/404 (25.74%)   53/197 (26.90%) 
Blood and lymphatic system disorders     
Neutropenia † 1  2/404 (0.50%)  0/197 (0.00%) 
Anaemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Febrile neutropenia † 1  1/404 (0.25%)  0/197 (0.00%) 
Thrombocytopenia † 1  1/404 (0.25%)  0/197 (0.00%) 
Cardiac disorders     
Cardiac failure † 1  2/404 (0.50%)  1/197 (0.51%) 
Atrial fibrillation † 1  1/404 (0.25%)  0/197 (0.00%) 
Cardiac arrest † 1  1/404 (0.25%)  1/197 (0.51%) 
Cardiovascular disorder † 1  1/404 (0.25%)  0/197 (0.00%) 
Pericardial effusion † 1  1/404 (0.25%)  2/197 (1.02%) 
Acute coronary syndrome † 1  0/404 (0.00%)  1/197 (0.51%) 
Myocardial infarction † 1  0/404 (0.00%)  1/197 (0.51%) 
Eye disorders     
Diplopia † 1  1/404 (0.25%)  0/197 (0.00%) 
Optic neuropathy † 1  1/404 (0.25%)  0/197 (0.00%) 
Gastrointestinal disorders     
Diarrhoea † 1  16/404 (3.96%)  7/197 (3.55%) 
Vomiting † 1  10/404 (2.48%)  5/197 (2.54%) 
Nausea † 1  8/404 (1.98%)  3/197 (1.52%) 
Abdominal pain † 1  4/404 (0.99%)  0/197 (0.00%) 
Abdominal pain upper † 1  3/404 (0.74%)  0/197 (0.00%) 
Constipation † 1  2/404 (0.50%)  2/197 (1.02%) 
Abdominal distension † 1  1/404 (0.25%)  0/197 (0.00%) 
Abdominal pain lower † 1  1/404 (0.25%)  0/197 (0.00%) 
Gastrointestinal haemorrhage † 1  1/404 (0.25%)  0/197 (0.00%) 
Intestinal perforation † 1  1/404 (0.25%)  0/197 (0.00%) 
Pancreatitis † 1  1/404 (0.25%)  0/197 (0.00%) 
Small intestinal obstruction † 1  1/404 (0.25%)  2/197 (1.02%) 
Stomatitis † 1  1/404 (0.25%)  0/197 (0.00%) 
Ascites † 1  0/404 (0.00%)  1/197 (0.51%) 
Enteritis † 1  0/404 (0.00%)  1/197 (0.51%) 
Enterocolitis † 1  0/404 (0.00%)  2/197 (1.02%) 
Oesophageal varices haemorrhage † 1  0/404 (0.00%)  2/197 (1.02%) 
General disorders     
Fatigue † 1  3/404 (0.74%)  2/197 (1.02%) 
Sudden death † 1  2/404 (0.50%)  0/197 (0.00%) 
General physical health deterioration † 1  1/404 (0.25%)  0/197 (0.00%) 
Multiple organ dysfunction syndrome † 1  1/404 (0.25%)  1/197 (0.51%) 
Non-cardiac chest pain † 1  1/404 (0.25%)  0/197 (0.00%) 
Pyrexia † 1  1/404 (0.25%)  1/197 (0.51%) 
Oedema peripheral † 1  0/404 (0.00%)  1/197 (0.51%) 
Pain † 1  0/404 (0.00%)  1/197 (0.51%) 
Systemic inflammatory response syndrome † 1  0/404 (0.00%)  1/197 (0.51%) 
Hepatobiliary disorders     
Cholecystitis † 1  2/404 (0.50%)  0/197 (0.00%) 
Hyperbilirubinaemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Infections and infestations     
Pneumonia † 1  4/404 (0.99%)  2/197 (1.02%) 
Sepsis † 1  4/404 (0.99%)  1/197 (0.51%) 
Gastroenteritis † 1  3/404 (0.74%)  1/197 (0.51%) 
Upper respiratory tract infection † 1  2/404 (0.50%)  1/197 (0.51%) 
Anal abscess † 1  1/404 (0.25%)  0/197 (0.00%) 
Cellulitis † 1  1/404 (0.25%)  1/197 (0.51%) 
Clostridium difficile colitis † 1  1/404 (0.25%)  2/197 (1.02%) 
Infected skin ulcer † 1  1/404 (0.25%)  0/197 (0.00%) 
Influenza † 1  1/404 (0.25%)  1/197 (0.51%) 
Lung infection † 1  1/404 (0.25%)  0/197 (0.00%) 
Oesophageal candidiasis † 1  1/404 (0.25%)  0/197 (0.00%) 
Oral candidiasis † 1  1/404 (0.25%)  0/197 (0.00%) 
Peritonitis † 1  1/404 (0.25%)  0/197 (0.00%) 
Septic shock † 1  1/404 (0.25%)  0/197 (0.00%) 
Soft tissue infection † 1  1/404 (0.25%)  0/197 (0.00%) 
Urinary tract infection † 1  1/404 (0.25%)  0/197 (0.00%) 
Gastroenteritis viral † 1  0/404 (0.00%)  1/197 (0.51%) 
Klebsiella sepsis † 1  0/404 (0.00%)  1/197 (0.51%) 
Large intestine infection † 1  0/404 (0.00%)  1/197 (0.51%) 
Respiratory tract infection viral † 1  0/404 (0.00%)  1/197 (0.51%) 
Urosepsis † 1  0/404 (0.00%)  1/197 (0.51%) 
Injury, poisoning and procedural complications     
Fall † 1  2/404 (0.50%)  0/197 (0.00%) 
Spinal fracture † 1  2/404 (0.50%)  0/197 (0.00%) 
Ankle fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Foot fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Patella fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Radius fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Spinal compression fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Sternal fracture † 1  1/404 (0.25%)  0/197 (0.00%) 
Investigations     
Ejection fraction decreased † 1  5/404 (1.24%)  2/197 (1.02%) 
Blood bilirubin increased † 1  1/404 (0.25%)  1/197 (0.51%) 
White blood cell count decreased † 1  1/404 (0.25%)  0/197 (0.00%) 
Electrocardiogram QT prolonged † 1  0/404 (0.00%)  1/197 (0.51%) 
Metabolism and nutrition disorders     
Dehydration † 1  4/404 (0.99%)  0/197 (0.00%) 
Decreased appetite † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypercalcaemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypernatraemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypoglycaemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypokalaemia † 1  1/404 (0.25%)  4/197 (2.03%) 
Hyponatraemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypophosphataemia † 1  1/404 (0.25%)  0/197 (0.00%) 
Lactic acidosis † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypovolaemia † 1  0/404 (0.00%)  1/197 (0.51%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  3/404 (0.74%)  0/197 (0.00%) 
Muscular weakness † 1  3/404 (0.74%)  1/197 (0.51%) 
Fracture nonunion † 1  1/404 (0.25%)  0/197 (0.00%) 
Musculoskeletal chest pain † 1  1/404 (0.25%)  0/197 (0.00%) 
Pain in extremity † 1  1/404 (0.25%)  0/197 (0.00%) 
Back pain † 1  0/404 (0.00%)  1/197 (0.51%) 
Bone pain † 1  0/404 (0.00%)  1/197 (0.51%) 
Rheumatoid arthritis † 1  0/404 (0.00%)  1/197 (0.51%) 
Spinal disorder † 1  0/404 (0.00%)  1/197 (0.51%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain † 1  2/404 (0.50%)  1/197 (0.51%) 
Acral lentiginous melanoma † 1  1/404 (0.25%)  0/197 (0.00%) 
Malignant pleural effusion † 1  1/404 (0.25%)  0/197 (0.00%) 
Pyogenic granuloma † 1  1/404 (0.25%)  0/197 (0.00%) 
Nervous system disorders     
Seizure † 1  7/404 (1.73%)  2/197 (1.02%) 
Depressed level of consciousness † 1  2/404 (0.50%)  0/197 (0.00%) 
Headache † 1  2/404 (0.50%)  3/197 (1.52%) 
Hemiparesis † 1  2/404 (0.50%)  0/197 (0.00%) 
Syncope † 1  2/404 (0.50%)  1/197 (0.51%) 
Aphasia † 1  1/404 (0.25%)  1/197 (0.51%) 
Cauda equina syndrome † 1  1/404 (0.25%)  0/197 (0.00%) 
Central nervous system necrosis † 1  1/404 (0.25%)  0/197 (0.00%) 
Encephalopathy † 1  1/404 (0.25%)  0/197 (0.00%) 
Epilepsy † 1  1/404 (0.25%)  0/197 (0.00%) 
Haemorrhagic stroke † 1  1/404 (0.25%)  0/197 (0.00%) 
Spinal cord compression † 1  1/404 (0.25%)  0/197 (0.00%) 
Brain oedema † 1  0/404 (0.00%)  1/197 (0.51%) 
Cerebral infarction † 1  0/404 (0.00%)  1/197 (0.51%) 
Facial paralysis † 1  0/404 (0.00%)  1/197 (0.51%) 
Generalised tonic-clonic seizure † 1  0/404 (0.00%)  1/197 (0.51%) 
Psychiatric disorders     
Confusional state † 1  1/404 (0.25%)  1/197 (0.51%) 
Mental status changes † 1  1/404 (0.25%)  2/197 (1.02%) 
Renal and urinary disorders     
Acute kidney injury † 1  1/404 (0.25%)  1/197 (0.51%) 
Ureterolithiasis † 1  1/404 (0.25%)  0/197 (0.00%) 
Urinary retention † 1  1/404 (0.25%)  0/197 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1  5/404 (1.24%)  6/197 (3.05%) 
Pulmonary embolism † 1  4/404 (0.99%)  3/197 (1.52%) 
Pleural effusion † 1  3/404 (0.74%)  6/197 (3.05%) 
Pneumothorax † 1  2/404 (0.50%)  0/197 (0.00%) 
Respiratory failure † 1  2/404 (0.50%)  1/197 (0.51%) 
Acute respiratory failure † 1  1/404 (0.25%)  1/197 (0.51%) 
Choking † 1  1/404 (0.25%)  0/197 (0.00%) 
Hypoxia † 1  1/404 (0.25%)  1/197 (0.51%) 
Pneumothorax spontaneous † 1  1/404 (0.25%)  0/197 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatomyositis † 1  1/404 (0.25%)  0/197 (0.00%) 
Vascular disorders     
Hypotension † 1  2/404 (0.50%)  0/197 (0.00%) 
Lymphoedema † 1  1/404 (0.25%)  0/197 (0.00%) 
Orthostatic hypotension † 1  1/404 (0.25%)  1/197 (0.51%) 
Vena cava thrombosis † 1  0/404 (0.00%)  1/197 (0.51%) 
1
Term from vocabulary, MedDRA v22.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tuc+Cap+Tra Pbo+Cap+Tra
Affected / at Risk (%) Affected / at Risk (%)
Total   400/404 (99.01%)   190/197 (96.45%) 
Blood and lymphatic system disorders     
Anaemia † 1  80/404 (19.80%)  23/197 (11.68%) 
Neutropenia † 1  32/404 (7.92%)  17/197 (8.63%) 
Thrombocytopenia † 1  25/404 (6.19%)  11/197 (5.58%) 
Eye disorders     
Dry eye † 1  22/404 (5.45%)  9/197 (4.57%) 
Gastrointestinal disorders     
Diarrhoea † 1  325/404 (80.45%)  105/197 (53.30%) 
Nausea † 1  236/404 (58.42%)  85/197 (43.15%) 
Vomiting † 1  144/404 (35.64%)  48/197 (24.37%) 
Stomatitis † 1  103/404 (25.50%)  28/197 (14.21%) 
Abdominal pain † 1  59/404 (14.60%)  31/197 (15.74%) 
Constipation † 1  59/404 (14.60%)  37/197 (18.78%) 
Dyspepsia † 1  43/404 (10.64%)  19/197 (9.64%) 
Abdominal pain upper † 1  27/404 (6.68%)  18/197 (9.14%) 
Gastrooesophageal reflux disease † 1  23/404 (5.69%)  6/197 (3.05%) 
Abdominal distension † 1  21/404 (5.20%)  9/197 (4.57%) 
Dry mouth † 1  21/404 (5.20%)  5/197 (2.54%) 
General disorders     
Fatigue † 1  181/404 (44.80%)  85/197 (43.15%) 
Oedema peripheral † 1  42/404 (10.40%)  19/197 (9.64%) 
Asthenia † 1  29/404 (7.18%)  15/197 (7.61%) 
Pyrexia † 1  20/404 (4.95%)  7/197 (3.55%) 
Hepatobiliary disorders     
Hyperbilirubinaemia † 1  26/404 (6.44%)  8/197 (4.06%) 
Infections and infestations     
Urinary tract infection † 1  42/404 (10.40%)  15/197 (7.61%) 
Upper respiratory tract infection † 1  37/404 (9.16%)  14/197 (7.11%) 
Nasopharyngitis † 1  20/404 (4.95%)  12/197 (6.09%) 
Paronychia † 1  20/404 (4.95%)  3/197 (1.52%) 
Injury, poisoning and procedural complications     
Fall † 1  22/404 (5.45%)  8/197 (4.06%) 
Investigations     
Aspartate aminotransferase increased † 1  86/404 (21.29%)  22/197 (11.17%) 
Alanine aminotransferase increased † 1  81/404 (20.05%)  13/197 (6.60%) 
Blood bilirubin increased † 1  75/404 (18.56%)  20/197 (10.15%) 
Blood creatinine increased † 1  56/404 (13.86%)  3/197 (1.52%) 
Weight decreased † 1  54/404 (13.37%)  11/197 (5.58%) 
Blood alkaline phosphatase increased † 1  25/404 (6.19%)  6/197 (3.05%) 
White blood cell count decreased † 1  18/404 (4.46%)  10/197 (5.08%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  100/404 (24.75%)  39/197 (19.80%) 
Hypokalaemia † 1  64/404 (15.84%)  23/197 (11.68%) 
Hypomagnesaemia † 1  35/404 (8.66%)  9/197 (4.57%) 
Dehydration † 1  29/404 (7.18%)  10/197 (5.08%) 
Hypophosphataemia † 1  24/404 (5.94%)  10/197 (5.08%) 
Hyperglycaemia † 1  23/404 (5.69%)  3/197 (1.52%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  57/404 (14.11%)  9/197 (4.57%) 
Back pain † 1  45/404 (11.14%)  23/197 (11.68%) 
Pain in extremity † 1  41/404 (10.15%)  17/197 (8.63%) 
Muscle spasms † 1  38/404 (9.41%)  5/197 (2.54%) 
Myalgia † 1  26/404 (6.44%)  9/197 (4.57%) 
Nervous system disorders     
Headache † 1  86/404 (21.29%)  38/197 (19.29%) 
Peripheral sensory neuropathy † 1  47/404 (11.63%)  12/197 (6.09%) 
Dizziness † 1  45/404 (11.14%)  27/197 (13.71%) 
Dysgeusia † 1  30/404 (7.43%)  5/197 (2.54%) 
Paraesthesia † 1  20/404 (4.95%)  8/197 (4.06%) 
Psychiatric disorders     
Insomnia † 1  33/404 (8.17%)  17/197 (8.63%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  57/404 (14.11%)  23/197 (11.68%) 
Epistaxis † 1  47/404 (11.63%)  10/197 (5.08%) 
Dyspnoea † 1  46/404 (11.39%)  21/197 (10.66%) 
Oropharyngeal pain † 1  25/404 (6.19%)  8/197 (4.06%) 
Rhinorrhoea † 1  21/404 (5.20%)  5/197 (2.54%) 
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome † 1  256/404 (63.37%)  104/197 (52.79%) 
Dry skin † 1  38/404 (9.41%)  18/197 (9.14%) 
Skin hyperpigmentation † 1  34/404 (8.42%)  11/197 (5.58%) 
Rash maculo-papular † 1  27/404 (6.68%)  10/197 (5.08%) 
Pruritus † 1  23/404 (5.69%)  12/197 (6.09%) 
1
Term from vocabulary, MedDRA v22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Seattle Genetics, Inc.
Phone: (855)473-2436
EMail: medinfo@seagen.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT02614794    
Other Study ID Numbers: ONT-380-206
2015-002801-12 ( EudraCT Number )
First Submitted: November 20, 2015
First Posted: November 25, 2015
Results First Submitted: September 4, 2020
Results First Posted: September 28, 2020
Last Update Posted: September 13, 2022