Phase 1b/2 Trial of AMG386 With Pemetrexed and Carboplatin in Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this phase 1b/2 study is to estimate the treatment effect of study drug measuring progression free survival.

Detailed Description
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To evaluate the incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicity in subjects with metastatic non-squamous non-small cell lung cancer (NSCLC) treated with AMG 386 in combination with pemetrexed and carboplatin

Official Title
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A Phase 1b/2 Trial of AMG 386 in Combination With Pemetrexed and Carboplatin as First Line Treatment of Metastatic Non-Squamous Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AMG 386
* Drug: AMG 386
* Drug: AMG 386 Placebo
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, unresectable stage IV non-squamous non small cell lung cancer (NSCLC) Radiographically evaluable disease (measurable or non-measurable) per RECIST 1.1 with modifications Adequate hematological, renal, and hepatic function, normal coagulation profile, calculated CrCL ≥ 45 mL/min Other criteria may apply Exclusion Criteria: Any prior chemotherapy or targeted therapy for non-squamous NSCLC Subjects with adenosquamous histology or any histology subtype containing greater than 10% squamous cells Subjects with an epidermal growth factor receptor (EGFR) mutation sensitive to treatment with a tyrosine kinase inhibitor (TKI) Subjects with known anaplastic lymphoma kinase (EML4-ALK) translocations History or presence of central nervous system metastases Central (chest) radiation therapy within 28 days prior to enrollment/randomization, radiation therapy to any other site(s) within 14 days prior to enrollment/randomization History of pulmonary hemorrhage or gross hemoptysis within 6 months History of arterial or venous thromboembolism within 12 months History of clinically significant bleeding within 6 months Clinically significant cardiovascular disease within 12 months Other criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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 A<br>Arm A: AMG 386 placebo IV QW, pemetrexed 500 mg/m2 IV Q3W, carboplatin AUC 6 IV Q3W, for up to 6 cycles | Drug: AMG 386 Placebo<br>* AMG 386 Placebo<br>Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2<br>Drug: Carboplatin<br>* Carboplatin AUC 6<br>|
| Experimental: Arm B<br>Arm B: AMG 386 15 mg/kg IV QW, pemetrexed 500 mg/m2 IV Q3W, carboplatin AUC 6 IV Q3W, for up to 6 cycles | Drug: AMG 386<br>* 15mg/kg<br>Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2<br>Drug: Carboplatin<br>* Carboplatin AUC 6<br>|
| Experimental: Arm C<br>Arm C: AMG 386 30 mg/kg IV QW, pemetrexed 500 mg/m2 IV Q3W, carboplatin AUC 6 IV Q3W, for up to 6 cycles | Drug: AMG 386<br>* 30 mg/kg<br>Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2<br>Drug: Carboplatin<br>* Carboplatin AUC 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Subjects will be evaluated for progression free survival. | Incidence of adverse events and clinical laboratory abnormalities defined as a DLT |