A Study of MM-121 Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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A Phase 1-2 study of MM-121 in combination with standard therapy for non-small cell lung cancer (NSCLC).

Detailed Description
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Phase 1: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to evaluate the safety, tolerability and recommended Phase 2 dose of MM-121 in combination with standard therapy. Phase 2: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to estimate the progression-free survival of the MM-121 + standard therapy.

Official Title
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A Phase 1-2 Trial of MM-121 in Combination With Erlotinib in Three Groups of Patients With Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: MM-121
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced or metastatic non-small cell lung cancer. Patients must be >/= 18 years of age. Patients must have adequate Performance Status (PS) as measured by ECOG and adequate end organ function. Exclusion Criteria: Patients with a recent history (within 5 years) of another malignancy. Patients who are pregnant or nursing. Patients with clinically significant heart failure. Patients with clinically significant eye or gastrointestinal abnormalities.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose-Escalation<br>Escalating doses of MM-121 (QOW IV) and erlotinib (daily PO) | Drug: MM-121<br>* MM-121 (SAR256212) = intravenous solution<br>* Other names: SAR256212;Drug: Erlotinib<br>* erlotinib = daily oral tablet<br>* Other names: Tarceva;|
| Active Comparator: Phase 2: Control<br>Erlotinib (daily) | Drug: Erlotinib<br>* erlotinib = daily oral tablet<br>* Other names: Tarceva;|
| Experimental: Phase 2: Treatment<br>MM-121 (QOW IV) and erlotinib (daily PO) | Drug: MM-121<br>* MM-121 (SAR256212) = intravenous solution<br>* Other names: SAR256212;Drug: Erlotinib<br>* erlotinib = daily oral tablet<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: To Determine the Recommended Phase 2 Dose of the MM-121 + Erlotinib Combination Based Upon Either the Maximum Tolerated Dose (MTD) or the Maximum Feasible Dose of the Combination in Patients With NSCLC. | To establish the safety of escalating doses of MM-121 in combination with erlotinib in order to determine the recommended phase 2 dose of the combination for the second part of the study. 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. | From date of first dose to 30 days after termination, the longest 175 weeks | 
| Phase 1: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities | Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was used as the recommended Phase 2 dose. | From date of first dose to 30 days after termination, the longest 175 weeks | 
| Phase 2: Progression-free Survival of the MM-121 + Erlotinib Combination | This was a time-to-event measure using Progression-Free Survival (PFS) comparing MM-121 + erlotinib vs.erlotinib alone. Progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival was defined as the number of weeks from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD). | Time from first dose to date of progression, with a median of 8.1 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ErbB3 antagonist, Non-Small Cell Lung Cancer, NSCLC, Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer, Lung Cancer, Erlotinib, Tarceva, MM-121, ErbB3, Her3, Epidermal Growth Factor Receptor, anti-ErbB3 human monoclonal antibody