A Study of MEHD7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of The Head And Neck

Phase 2

Completed

Brief Summary: This phase II, open-label, randomized study will evaluate the efficacy and safety of MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck who have progressed during or following platinum-based chemotherapy. Patients will be randomized to receive either MEHD7945A 1100 mg intravenously (iv) every 2 weeks or cetuximab 400 mg/m2 iv loading dose followed by 250 mg/m2 iv weekly. Patients treated with cetuximab (Arm B) may cross-over to MEHD7945A (Arm A) upon central confirmation of progressive disease and upon meeting eligibility criteria. Anticipated time on study treatment is until disease progression or intolerable toxicity occurs.

Recruitment & Eligibility

Inclusion Criteria

Adult patients, >/= 18 years of age
Histologically confirmed Stage III or IV recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)
Progressive disease on or after first-line platinum-based chemotherapy regimen for R/M SCCHN (maximum of 6 cycles)
No more than one platinum-based chemotherapy regimen for R/M SCCHN is allowed
Prior platinum-based treatment as definitive chemo/radiotherapy for locally advanced disease is allowed if completed/terminated >/= 6 months before the platinum-based regimen for R/M SCCHN
Consent to provide archival tumor tissue for biomarker testing
Measurable disease per RECIST v1.1
ECOG performance status of 0, 1 or 2
Adequate hematologic, renal and liver function

Exclusion Criteria

Nasopharyngeal cancer
Prior treatment with an investigational or approved agent for the purpose of inhibiting HER family members
This includes but is not limited to cetuximab, panitumumab, erlotinib, geftinib, and lapatinib
Prior treatment with an EGFR inhibitor is allowed if it was administered as part of definitive therapy for locally advanced disease and completed >/=1 year before study enrollment
Leptomeningeal disease as the only manifestation of the current malignancy
Active infection requiring iv antibiotics
Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs
Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures)
History of heart failure or serious cardiac arrhythmia
History of myocardial infarction within 6 months of Cycle 1, Day 1
Clinically significant liver disease, including active viral, alcoholic or other hepatitis, cirrhosis, or current alcohol abuse
HIV infection
Primary central nervous system (CNS) malignancy or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
Pregnant or lactating women
Malignancies other than SCCHN within 5 years prior to randomization, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix

Arm && Interventions

Group	Intervention	Description
A: MEHD7945A	MEHD7945A	-
B: Cetuximab	cetuximab	-

Primary Outcome Measures

Name	Time	Method
Progression-free survival (tumor assessments according to RECIST criteria)	approximately 24 months

Secondary Outcome Measures

Name	Time	Method
Objective response: complete response or partial response	approximately 24 months
Immunogenicity: anti-MEHD7945A levels	Pre-dose on Day 1 of Cycles 1 and 4, and at treatment completion
Duration of objective response	approximately 24 months
Disease control: complete response, partial response or stable disease	approximately 24 months
Time to disease progression	approximately 24 months
Overall survival	approximately 24 months
Safety: Incidence of adverse events	approximately 24 months
Pharmacokinetics: Cmax/Cmin	Pre-dose and 30 min after end of infusion on Day 1 of Cycles 1, 2, 3, and 4, and at treatment completion