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A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers

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: NCT01451632
Recruitment Status : Completed
First Posted : October 13, 2011
Results First Posted : September 8, 2016
Last Update Posted : September 8, 2016
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Colorectal Cancer
Squamous Cell Head and Neck Cancer
Non-small Cell Lung Cancer
Triple Negative Breast Cancer
Other Tumors With EGFR Dependence
Interventions Drug: MM-121
Drug: Irinotecan
Drug: Cetuximab
Enrollment 48
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2a Part 1: Cohort 2b Part 1: Cohort 3a Part 1: Cohort 3b Part 1: Cohort 4 Part 1: Expansion Cohort Part 2: Cohort 1 Part 2: Cohort 2 Part 2: Expansion Cohort
Hide Arm/Group Description MM-121: 12 mg/kg IV weekly in 4-week cycles Cetuximab: 400 mg/m2 IV one-time loading dose followed by 200 mg/m2 IV weekly maintenance doses MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW MM-121: 40 mg/kg one time loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 one-time loading dose followed by 250 mg/m2 maintenance IV QW MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

Period Title: Overall Study
Started 8 4 3 3 4 4 8 6 4 4
Completed 8 4 3 3 4 4 8 6 4 4
Not Completed 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan Total
Hide Arm/Group Description

increasing doses of weekly MM-121 + weekly cetuximab

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

increasing doses of irinotecan + the RP2D of MM121 + cetuximab as determined in Part 1

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Irinotecan: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Total of all reporting groups
Overall Number of Baseline Participants 34 14 48
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 14 participants 48 participants
56.1  (14.19) 56.6  (11.38) 56.35  (12.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 14 participants 48 participants
Female
13
  38.2%
9
  64.3%
22
  45.8%
Male
21
  61.8%
5
  35.7%
26
  54.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 14 participants 48 participants
Hispanic or Latino
2
   5.9%
1
   7.1%
3
   6.3%
Not Hispanic or Latino
31
  91.2%
13
  92.9%
44
  91.7%
Unknown or Not Reported
1
   2.9%
0
   0.0%
1
   2.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 14 participants 48 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   8.8%
0
   0.0%
3
   6.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   8.8%
0
   0.0%
3
   6.3%
White
26
  76.5%
13
  92.9%
39
  81.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   5.9%
1
   7.1%
3
   6.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 34 participants 14 participants 48 participants
34 14 48
1.Primary Outcome
Title Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Cetuximab and the MM-121 Plus Cetuximab Plus Irinotecan Combination
Hide Description To establish the safety of escalating doses of MM-121 in combination with cetuximab or in combination with cetuximab and irinotecan in order to determine the recommended phase 2 dose.. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
Time Frame From date of first dose to 30 days after termination, the longest 48.1 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients participating in dose escalation
Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2a Part 1: Cohort 2b Part 1: Cohort 3a Part 1: Cohort 3b Part 1: Cohort 4 Part 2: Cohort 1 Part 2: Cohort 2
Hide Arm/Group Description:
MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW Irinotecan: 180 mg/m2 IV Q2W
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW Irinotecan: 180 mg/m2 IV Q2W
Overall Number of Participants Analyzed 8 4 3 3 4 4 6 4
Measure Type: Number
Unit of Measure: participants reporting DLTs
1 0 0 0 0 0 1 2
2.Primary Outcome
Title To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s) (Via Recording of Maximum Tolerated Dose (MTD)): MM-121 Doses
Hide Description

Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD

Part 1:

Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW

Part 2:

Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2

Time Frame From date of first dose to 30 days after termination, the longest 48.1 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients participating in dose-escalation portion (excluding expansion cohort patients who were not evaluated for DLTs) MTD of cetuximab and irinotecan for the combination(s) are presented in a separate endpoint entry
Arm/Group Title Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Hide Arm/Group Description:

increasing doses of weekly MM-121 + weekly cetuximab

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

increasing doses of irinotecan + the RP2D of MM121 + cetuximab as determined in Part 1

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Irinotecan: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Overall Number of Participants Analyzed 26 10
Measure Type: Number
Unit of Measure: mg/kg
MM-121 loading dose 40 NA [1] 
MM-121 maintenance dose 20 20
[1]
The addition of the loading dose was determined to be a maximum tolerated dose, and is not included in the RP2D
3.Primary Outcome
Title To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s): Cetuximab and Irinotecan
Hide Description

Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD

Part 1:

Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW

Part 2:

Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2

Time Frame From date of first dose to 30 days after termination, the longest 48.1 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients participating in dose-escalation portion (excluding expansion cohort patients who were not evaluated for DLTs and thus not included in determining MTD/RP2D) NOTE: MTD of MM-121 provided in separate endpoint entry
Arm/Group Title Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Hide Arm/Group Description:

increasing doses of weekly MM-121 + weekly cetuximab

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

increasing doses of irinotecan + the RP2D of MM121 + cetuximab as determined in Part 1

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Irinotecan: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Overall Number of Participants Analyzed 26 10
Measure Type: Number
Unit of Measure: mg/m2
Cetuximab loading dose 400 400
Cetuximab maintenance dose 250 250
Irinotecan NA [1]  180
[1]
Irinotecan was not administered during Part 1
4.Secondary Outcome
Title Objective Response Rate
Hide Description To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR.
Time Frame Patients were assessed for objective response from time of first dose through treatment termination, the longest treatment duration being 48.1 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2a Part 1: Cohort 2b Part 1: Cohort 3a Part 1: Cohort 3b Part 1: Cohort 4 Part 1: Expansion Cohort Part 2: Cohort 1 Part 2: Cohort 2 Part 2: Expansion Cohort
Hide Arm/Group Description:
MM-121: 12 mg/kg IV weekly in 4-week cycles Cetuximab: 400 mg/m2 IV one-time loading dose followed by 200 mg/m2 IV weekly maintenance doses
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg one time loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 one-time loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

Overall Number of Participants Analyzed 8 4 3 3 4 4 8 6 4 4
Measure Type: Number
Unit of Measure: participants with objective response
1 0 0 0 0 0 1 1 0 0
5.Secondary Outcome
Title Pharmacokinetics
Hide Description Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)
Time Frame Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 1: 12 mg/kg Part 1: 20 mg/kg Part 1: 40/20 mg/kg Part 2: 20 mg/kg Part 2: 40/20 mg/kg
Hide Arm/Group Description:
MM-121 mg/kg plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 20 mg/kg Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 20 mg/kg plus cetuximab at 400/250 mg/m2 plus irinotecan at 180 mg/m2
MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses plus cetuximab 400/250 mg/m2 plus irinotecan 180 mg/m2
Overall Number of Participants Analyzed 11 8 15 10 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
316.8
(23.6%)
611.0
(45.8%)
794.1
(58.2%)
505.8
(10.2%)
1278.2
(25%)
6.Secondary Outcome
Title Pharmacokinetic Parameters of MM-121
Hide Description Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the AUClast. Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)
Time Frame Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121
Hide Outcome Measure Data
Hide Analysis Population Description
Data presented by dose level of MM-121, regardless of the cohort (i.e. 15 patients in Part 1 were administered the 40/20 dose level of MM-121: 3 in cohort 3b, 4 in cohort 4, and 8 in the Part 1 expansion)
Arm/Group Title Part 1: 12 mg/kg Part 1: 20 mg/kg Part 1: 40/20 mg/kg Part 2: 20 mg/kg Part 2: 40/20 mg/kg
Hide Arm/Group Description:
MM-121 mg/kg plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 20 mg/kg Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2
MM-121: 20 mg/kg plus cetuximab at 400/250 mg/m2 plus irinotecan at 180 mg/m2
MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses plus cetuximab 400/250 mg/m2 plus irinotecan 180 mg/m2
Overall Number of Participants Analyzed 11 8 15 10 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr* ug/mL
24190.5
(22.0%)
53063.1
(46.1%)
91111.9
(39.9%)
47681.5
(14.2%)
98387.7
(16.2%)
7.Secondary Outcome
Title Immunogenicity
Hide Description Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
Time Frame Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 48.1 weeks, and a collection was made post-infusion in any case of infusion reaction
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 1: Cohort 1 Part 1: Cohort 2a Part 1: Cohort 2b Part 1: Cohort 3a Part 1: Cohort 3b Part 1: Cohort 4 Part 1: Expansion Cohort Part 2: Cohort 1 Part 2: Cohort 2 Part 2: Expansion Cohort
Hide Arm/Group Description:
MM-121: 12 mg/kg IV weekly in 4-week cycles Cetuximab: 400 mg/m2 IV one-time loading dose followed by 200 mg/m2 IV weekly maintenance doses
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW
MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg one time loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 one-time loading dose followed by 250 mg/m2 maintenance IV QW
MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

Overall Number of Participants Analyzed 8 4 3 3 4 4 8 6 4 4
Measure Type: Number
NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1] 
[1]
The very small number of patients in each cohort and the very low levels of positivity resulted in a non-reportable value
Time Frame AEs were collected from a patient's first dose until 30 days after treatment termination. SAEs were collected from time of informed consent until 30 days after termination. If related, events could be reported at any time after termination.
Adverse Event Reporting Description All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination
 
Arm/Group Title Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Hide Arm/Group Description

increasing doses of weekly MM-121 + weekly cetuximab

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

increasing doses of irinotecan + the RP2D of MM121 + cetuximab as determined in Part 1

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Irinotecan: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

All-Cause Mortality
Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Affected / at Risk (%) Affected / at Risk (%)
Total   15/34 (44.12%)   6/14 (42.86%) 
Blood and lymphatic system disorders     
Neutropenia * 1  0/34 (0.00%)  1/14 (7.14%) 
Cardiac disorders     
Pericardial effusion * 1  1/34 (2.94%)  1/14 (7.14%) 
Supraventricular tachycardia * 1  1/34 (2.94%)  0/14 (0.00%) 
Cardiac Arrest * 1  0/34 (0.00%)  1/14 (7.14%) 
Gastrointestinal disorders     
Abdominal Pain * 1  1/34 (2.94%)  0/14 (0.00%) 
Constipation * 1  1/34 (2.94%)  0/14 (0.00%) 
Diarrhea * 1  1/34 (2.94%)  2/14 (14.29%) 
Intestinal Obstruction * 1  0/34 (0.00%)  1/14 (7.14%) 
Nausea * 1  0/34 (0.00%)  1/14 (7.14%) 
Stomatitis * 1  0/34 (0.00%)  1/14 (7.14%) 
Vomiting * 1  0/34 (0.00%)  1/14 (7.14%) 
General disorders     
Disease Progression * 1  1/34 (2.94%)  0/14 (0.00%) 
Mucosal Inflammation * 1  1/34 (2.94%)  0/14 (0.00%) 
Pyrexia * 1  1/34 (2.94%)  0/14 (0.00%) 
Non-cardiac chest pain * 1  0/34 (0.00%)  1/14 (7.14%) 
Hepatobiliary disorders     
Bile Duct Stenosis * 1  1/34 (2.94%)  0/14 (0.00%) 
Infections and infestations     
Abdominal Abscess * 1  1/34 (2.94%)  0/14 (0.00%) 
Device Related Infection * 1  1/34 (2.94%)  0/14 (0.00%) 
Lung Infection * 1  1/34 (2.94%)  0/14 (0.00%) 
Urinary Tract Infection * 1  0/34 (0.00%)  1/14 (7.14%) 
Injury, poisoning and procedural complications     
Infusion Related Reaction * 1  1/34 (2.94%)  0/14 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  0/34 (0.00%)  1/14 (7.14%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  1/34 (2.94%)  0/14 (0.00%) 
Pain in Extremity * 1  1/34 (2.94%)  0/14 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
metastases to central nervous system * 1  1/34 (2.94%)  0/14 (0.00%) 
Nervous system disorders     
Vocal cord paralysis * 1  1/34 (2.94%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism * 1  1/34 (2.94%)  1/14 (7.14%) 
Dyspnea * 1  0/34 (0.00%)  1/14 (7.14%) 
Respiratory Failure * 1  0/34 (0.00%)  1/14 (7.14%) 
Skin and subcutaneous tissue disorders     
Photosensitivity Reaction * 1  1/34 (2.94%)  0/14 (0.00%) 
Skin Ulcer * 1  1/34 (2.94%)  0/14 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis * 1  1/34 (2.94%)  0/14 (0.00%) 
Hypotension * 1  1/34 (2.94%)  0/14 (0.00%) 
Lyphoedema * 1  1/34 (2.94%)  0/14 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: MM-121 + Cetuximab Part 2: MM-121 + Cetuximab + Irinotecan
Affected / at Risk (%) Affected / at Risk (%)
Total   34/34 (100.00%)   14/14 (100.00%) 
Blood and lymphatic system disorders     
Anemia * 1 [1]  6/34 (17.65%)  1/14 (7.14%) 
Neutropenia * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Cardiac disorders     
Pericardial effusion * 1 [1]  2/34 (5.88%)  1/14 (7.14%) 
Tachycardia * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Cardiac Arrest * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Eye disorders     
Vision Blurred * 1 [1]  3/34 (8.82%)  1/14 (7.14%) 
Conjunctivitis * 1 [1]  2/34 (5.88%)  1/14 (7.14%) 
Lacrimation increased * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Ocular Hyperaemia * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Gastrointestinal disorders     
Diarrhea * 1 [1]  17/34 (50.00%)  13/14 (92.86%) 
Stomatitis * 1 [1]  9/34 (26.47%)  5/14 (35.71%) 
Nausea * 1 [1]  8/34 (23.53%)  8/14 (57.14%) 
Abdominal Pain * 1 [1]  7/34 (20.59%)  1/14 (7.14%) 
Constipation * 1 [1]  5/34 (14.71%)  0/14 (0.00%) 
Vomiting * 1 [1]  5/34 (14.71%)  5/14 (35.71%) 
Dyspepsia * 1 [1]  4/34 (11.76%)  1/14 (7.14%) 
Dry Mouth * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Hemorrhoids * 1 [1]  2/34 (5.88%)  2/14 (14.29%) 
Oral Pain * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Cheilitis * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Glossodynia * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Haematochezia * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Intestinal Obstruction * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
General disorders     
Fatigue * 1 [1]  22/34 (64.71%)  9/14 (64.29%) 
Mucosal Inflammation * 1 [1]  8/34 (23.53%)  4/14 (28.57%) 
Chills * 1 [1]  3/34 (8.82%)  0/14 (0.00%) 
Non-Cardiac Chest Pain * 1 [1]  2/34 (5.88%)  1/14 (7.14%) 
Asthenia * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Impaired healing * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Pyrexia * 1 [1]  4/34 (11.76%)  1/14 (7.14%) 
Infections and infestations     
Paronychia * 1 [1]  9/34 (26.47%)  0/14 (0.00%) 
Fungal Skin Infection * 1 [1]  2/34 (5.88%)  1/14 (7.14%) 
Urinary Tract Infection * 1 [1]  2/34 (5.88%)  3/14 (21.43%) 
Bronchitis * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Nail Infection * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Oral Infection * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Tinea Cruris * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Vulvovaginal Mycotic Infection * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Injury, poisoning and procedural complications     
Infusion Related Reaction * 1 [1]  5/34 (14.71%)  2/14 (14.29%) 
Post-Procedural Swelling * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Investigations     
Weight Decreased * 1 [1]  8/34 (23.53%)  7/14 (50.00%) 
Blood Magnesium Decreased * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
White Blood Cell Count Decreased * 1 [1]  0/34 (0.00%)  2/14 (14.29%) 
Neutrophil Count Decreased * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Metabolism and nutrition disorders     
Hypomagnesemia * 1 [1]  18/34 (52.94%)  5/14 (35.71%) 
Decreased Appetite * 1 [1]  12/34 (35.29%)  7/14 (50.00%) 
Hypokalemia * 1 [1]  10/34 (29.41%)  9/14 (64.29%) 
Hypocalcemia * 1 [1]  6/34 (17.65%)  4/14 (28.57%) 
Hypophosphatemia * 1 [1]  6/34 (17.65%)  3/14 (21.43%) 
Dehydration * 1 [1]  0/34 (0.00%)  6/14 (42.86%) 
Hypoalbuminemia * 1 [1]  0/34 (0.00%)  3/14 (21.43%) 
Hyponatremia * 1 [1]  0/34 (0.00%)  2/14 (14.29%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1 [1]  3/34 (8.82%)  0/14 (0.00%) 
Flank Pain * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Bone Pain * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Muscular Weakness * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Pain in Extremity * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Nervous system disorders     
Headache * 1 [1]  7/34 (20.59%)  0/14 (0.00%) 
Dygeusia * 1 [1]  4/34 (11.76%)  1/14 (7.14%) 
Ataxia * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Dizziness * 1 [1]  1/34 (2.94%)  2/14 (14.29%) 
Peripheral Neuropathy * 1 [1]  0/34 (0.00%)  2/14 (14.29%) 
Central Nervous System Lesion * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Neuralgia * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Peripheral Motor Neuropathy * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Psychiatric disorders     
Depression * 1 [1]  3/34 (8.82%)  0/14 (0.00%) 
Insomnia * 1 [1]  3/34 (8.82%)  1/14 (7.14%) 
Anxiety * 1 [1]  2/34 (5.88%)  1/14 (7.14%) 
Confusional State * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Renal and urinary disorders     
Pollakiuria * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1 [1]  6/34 (17.65%)  2/14 (14.29%) 
Epistaxis * 1 [1]  5/34 (14.71%)  1/14 (7.14%) 
Dyspnea * 1 [1]  3/34 (8.82%)  1/14 (7.14%) 
Rhinitis allergic * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Dysphonia * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Nasal Congestion * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Nasal Disorder * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Oropharyngeal Pain * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Pneumonitis * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Pulmonary Embolism * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Respiratory Failure * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Skin and subcutaneous tissue disorders     
Dermatitis Acneform * 1 [1]  18/34 (52.94%)  4/14 (28.57%) 
Rash Maculopapular * 1 [1]  10/34 (29.41%)  3/14 (21.43%) 
Rash * 1 [1]  8/34 (23.53%)  1/14 (7.14%) 
Dry Skin * 1 [1]  5/34 (14.71%)  3/14 (21.43%) 
Skin Fissures * 1 [1]  5/34 (14.71%)  1/14 (7.14%) 
Palmar-Plantar Erythrodysaesthesia Syndrome * 1 [1]  4/34 (11.76%)  4/14 (28.57%) 
Skin Ulcer * 1 [1]  3/34 (8.82%)  0/14 (0.00%) 
Pruritis * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Pruritis Generalized * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
Pain of skin * 1 [1]  0/34 (0.00%)  3/14 (21.43%) 
Alopecia * 1 [1]  0/34 (0.00%)  2/14 (14.29%) 
Nail Disorder * 1 [1]  0/34 (0.00%)  2/14 (14.29%) 
Erythema * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Nail Discoloration * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Rash Erythematous * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Rash Papular * 1 [1]  0/34 (0.00%)  1/14 (7.14%) 
Skin Irritation * 1 [1]  1/34 (2.94%)  1/14 (7.14%) 
Vascular disorders     
Deep Vein Thrombosis * 1 [1]  2/34 (5.88%)  0/14 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.1)
[1]
Any Relationship
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: Clinical Trial Manager
Organization: Merrimack Pharmaceuticals, Inc.
Phone: 617-441-1000
EMail: smathews@merrimack.com
Layout table for additonal information
Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01451632    
Other Study ID Numbers: MM-121-05-01-05 (TCD11696)
First Submitted: October 7, 2011
First Posted: October 13, 2011
Results First Submitted: July 12, 2016
Results First Posted: September 8, 2016
Last Update Posted: September 8, 2016