QUILT-2.017: Phase 1b/2 Study of AMG 479 in Combination With Paclitaxel and Carboplatin for 1st Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a global, multicenter, 2-part, open-label phase 1b and single-arm phase 2 study designed to evaluate the safety and efficacy of AMG 479 in combination with paclitaxel and carboplatin for the first-line treatment of advanced squamous non-small cell lung carcinoma.

Official Title
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A Phase 1b/2 Study of AMG 479 in Combination With Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer

Conditions
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Advanced Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: AMG 479
* Biological: AMG 479
* Drug: Carboplatin
* Biological: AMG 479
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced squamous NSCLC Measurable disease as defined per modified RECIST criteria ECOG performance status of 0 or 1 ≥18 years old Adequate glycemic function, for subjects with known diabetes Exclusion Criteria: Untreated or symptomatic central nervous system (CNS) metastases Prior anti-cancer therapy as follows: Any prior chemotherapy for squamous NSCLC; Any prior adjuvant or neoadjuvant chemotherapy for squamous NSCLC; Any prior chemoradiation for squamous NSCLC; Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for peripheral lesions≤14 days prior to enrollment for squamous NSCLC

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort 1<br>AMG 479 at 18 mg/kg in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for 24 months from study day 1 | Biological: AMG 479<br>* AMG 479 at 18mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on Day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 18 mg/kg IV monotherapy for up to 24 months from day 1<br>Drug: Carboplatin<br>* Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6<br>Drug: Paclitaxel<br>* Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6<br>|
| Experimental: Part 1 Cohort 2<br>AMG 479 at 12 mg/kg in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg monotherapy for 24 months from study day 1 | Biological: AMG 479<br>* AMG 479 at 12 mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 12 mg/kg IV monotherapy for up to 24 months from study day 1<br>Drug: Carboplatin<br>* Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6<br>Drug: Paclitaxel<br>* Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6<br>|
| Experimental: Part 2<br>AMG 479 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for 24 months from study day 1 (AMG 479 dose in Part 2 will be the final AMG 479 dose from Part 1) | Drug: Carboplatin<br>* Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6<br>Biological: AMG 479<br>* AMG 479 IV in combination with chemotherapy on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 24 months from study day 1. The AMG 479 dose to be used will be the final AMG 479 dose explored from Part 1<br>Drug: Paclitaxel<br>* Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicities |  | Part 1 Only | 
| Part 2: Objective Response Rate as per modified RECIST criteria by investigator review |  | Length of Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: The incidence of adverse events and laboratory abnormalities not defined as Dose Limiting Toxicities |  | Length of Study | 
| Part 1: Incidence of anti-AMG 479 antibody formation |  | Length of Study | 
| Part 2: Progression Free Survival, Time to Progression, Duration of Response, 1 & 2 year survival rates, and Overall Survival including subjects who received the final dose in Part 1 |  | Length of Study | 
| Part 2 Incidence of adverse events and laboratory abnormalities |  | Length of Study | 
| Incidence of anti-AMG479 antibody formation |  | Length of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 479, IGF-1R, Apoptosis, Monoclonal Antibody, Advanced Squamous Non-Small Cell Lung Cancer, antibody 1st-line