A Phase 1b/2 Study of AMG 655 in Combination With Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Part 1 is complete. Part 2 is a multi-center, randomized, double-blind, placebo-controlled, phase 2 segment that will commence upon identification of the maximum tolerated dose in part 1. The Primary objective of Part 2 of the study is to estimate efficacy in combination with carboplatin and paclitaxel. Subjects will be randomized at a 1:1:1 ratio to 1 of 3 treatment arms. Subjects in each of the 3 arms will receive up to 6 cycles of paclitaxel/carboplatin (at the same dose and schedule in part 1) in combination with either AMG 655 at the maximum tolerated dose (Arm 1), AMG 655 at a lower dose (Arm 2), or AMG 655 placebo (Arm 3) IV Q3W. Randomization will be stratified by ECOG (0 or 1) and disease stage (IIIb or IV/recurrent).

Official Title
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A Phase 1b/2 Study of AMG 655 in Combination With Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AMG 655
* Other: AMG 655 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease Related Histologically or cytologically confirmed non-small cell lung cancer. Subjects must have advanced non-small cell lung cancer defined as stage IIIB with malignant pleural effusion or stage IV or recurrent disease. Planning to receive up to 6 cycles of chemotherapy Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Demographic Men or women > 18 years of age Ethical Adequate Hematological, renal, hepatic and coagulation function General Plan to begin protocol specific therapy < 7 days after enrollment/randomization Exclusion Criteria: Disease Related Untreated or symptomatic central nervous system metastases. Subjects with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastasis and the subject is clinically stable and off corticosteroids for at least 14 days before enrollment/randomization. Prior chemotherapy as follows: Any prior chemotherapy for advanced non-small cell lung cancer Any prior adjuvant chemotherapy for non-small cell lung cancer < 52 weeks prior to enrollment/randomization. Adjuvant chemotherapy completed > 52 weeks prior to randomization is permitted. Any prior chemoradiation. Central (chest) radiation therapy < 28 days prior to randomization, radiation therapy for peripheral lesions < 14 days prior to enrollment/randomization Other abnormal medical conditions Documented myocardial infarction or unstable/uncontrolled cardiac condition History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders Major surgical procedure < 30 days prior to enrollment/randomization or not yet recovered from prior major surgery, Minor surgical procedure < 7 days prior to enrollment/randomization or not yet recovered from prior minor surgery

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 2<br>Low Dose AMG 655 with paclitaxel/carboplatin | Drug: AMG 655<br>* AMG 655 is a monoclonal antibody directed against TR-2.<br>* Other names: Placebo;|
| Placebo Comparator: Arm 3<br>Placebo with paclitaxel/carboplatin | Other: AMG 655 placebo<br>* Inactive dummy AMG 655 (to maintain blind)<br>|
| Experimental: Arm 1<br>AMG 655 High doseplus paclitaxel/carboplatin | Drug: AMG 655<br>* AMG 655 is a monoclonal antibody directed against TR-2.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | Until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate, duration of response, time to response, overall survival and incidence of adverse events and clinical laboratory abnormalities |  | Until disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-Small Cell Lung Cancer, Paclitaxel, Carboplatin, AMG 655