A Study of Onartuzumab (MetMAb) Versus Placebo in Combination With Paclitaxel Plus Platinum in Patients With Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with paclitaxel plus platinum in patients with incurable Stage IIIB or Stage IV squamous non-small cell lung cancer (NSCLC). Patients will be randomized to receive either onartuzumab (MetMAb) 15 mg/kg iv or placebo on Day 1 of each 21-day cycle in combination with 4 cycles of paclitaxel 200 mg/m2 iv and platinum (carboplatin/cisplatin) iv on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will continue with either onartuzumab (MetMAb) or placebo as maintenance therapy until disease progression or unacceptable toxicity occurs.

Official Title
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A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab (Metmab) in Combination With Paclitaxel + Cisplatin or Carboplatin as First-Line Treatment for Patients With Stage IIIb (T4 Disease) or IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: cisplatin/carboplatin
* Drug: onartuzumab
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Histologically or cytologically confirmed Stage III B or Stage IV squamous non-small cell lung cancer (NSCLC) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 No prior chemotherapy for squamous NSCLC Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown Radiographic evidence of disease Exclusion Criteria: Prior systemic treatment for Stage IIIB or IV squamous NSCLC NSCLC with histology classified as adenocarcinoma, large cell, mixed adenosquamous, or NSCLC not otherwise specified (NOS) Prior exposure to experimental treatment targeting either the HGF or Met pathway Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator Uncontrolled brain metastases and treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1 of Cycle 1 History of another malignancy in the previous 3 years except for prior history of in situ cancer or basal or squamous cell skin cancer Pregnant or lactating women Uncontrolled diabetes Impaired bone marrow, liver or renal function as defined by protocol Significant history of cardiovascular disease Positive for HIV infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MetMAb+paclitaxel+platinum<br> | Drug: cisplatin/carboplatin<br>* standard dose iv, Day 1 of each 21-day cycle, 4 cycles<br>Drug: onartuzumab<br>* 15 mg/kg iv, Day 1 of each 21-day cycle<br>* Other names: MetMAb;Drug: paclitaxel<br>* 200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles<br>|
| Active Comparator: Placebo+paclitaxel+platinum<br> | Drug: Placebo<br>* Matching onartuzumab (MetMAb) placebo iv, Day 1 of each 21-day cycle<br>Drug: cisplatin/carboplatin<br>* standard dose iv, Day 1 of each 21-day cycle, 4 cycles<br>Drug: paclitaxel<br>* 200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (tumor assessments according to RECIST criteria) |  | up to approximately 32 months | 
| Progression-free survival: Subgroup of patients with Met diagnostic-positive squamous NSCLC |  | up to approximately 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | up to approximately 32 months | 
| Overall response rate (tumor assessments according to RECIST criteria) |  | up to approximately 32 months | 
| Duration of response (time from first documented objective response to disease progression) |  | up to approximately 32 months | 
| Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks) |  | up to approximately 32 months | 
| Safety: Incidence of adverse events |  | up to approximately 32 months | 
| Pharmacokinetics: serum concentration (Cmin/Cmax) |  | Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and up to 2 years | 
| Plasma concentrations of paclitaxel/platinum |  | Pre- and post-dose on Day 1 of Cycles 1 and 4 | 
| Serum levels of anti-therapeutic antibodies (MetMAb ATAs) |  | Pre-dose Day 1 of Cycles 1, 2 and 4 |