Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

Phase 2

Completed

Interventions: Drug: 5-fluorouracil
Drug: Cetuximab
Drug: Irinotecan
Drug: MEHD7945A
Drug: Leucovorin

Brief Summary: This open-label, randomized, multicenter, Phase 2 study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI (folinic acid \[leucovorin\], 5-fluorouracil \[5-FU\], and irinotecan) chemotherapy as compared to cetuximab plus FOLFIRI in participants with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type mCRC who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Participants will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A or cetuximab. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with KRAS wild-type status
Progressive disease on or after first-line oxaliplatin-containing regimen for mCRC; participants must have received oxaliplatin-containing chemotherapy for greater than or equal to (>/=) 3 months; no more than one prior chemotherapy regimen for metastatic disease is allowed
Measurable disease per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate hematologic and end-organ function

Exclusion Criteria

Prior treatment with irinotecan
Prior treatment with an investigational or approved human epidermal growth factor receptor (HER)-targeted agent
Last anti-tumor therapy within 4 weeks prior to Cycle 1, Day 1
Leptomeningeal disease as the only manifestation of the current malignancy
Active infection requiring intravenous antibiotics
Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs
Current severe, uncontrolled systemic disease
Known human immunodeficiency virus (HIV) infection
Untreated/active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
Pregnant or lactating women
Malignancies other than colorectal cancer within 5 years prior to randomization, except for adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria	approximately 2 year

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	approximately 2 year
Maximum Observed Serum Concentration (Cmax) of MEHD7945A	Pre-dose and 30 minutes after end of infusion on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)
Minimum Observed Serum Concentration (Cmin) of MEHD7945A	Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)
Plasma Concentration of Irinotecan	Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Number of Participants With Anti-MEHD7945A Antibodies	Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years)
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria	approximately 2 year
Duration of Objective Response According to Modified RECIST v1.1 Criteria	approximately 2 year
Overall Survival (OS)	approximately 2 year
Plasma Concentration of 5-Fluorouracil	Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4