Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study aims to evaluate the safety and tolerability of AMG 160 and to evaluate the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D).

Official Title
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A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer, NSCLC

Intervention / Treatment
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* Drug: AMG 160


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has provided informed consent prior to initiation of any study specific activities/procedures. Histologically or cytologically confirmed stage 4 or recurrent non-squamous NSCLC (Part 1); histologically or cytologically. confirmed stage 4 or recurrent NSCLC (Part 2 only, squamous cell histology/cytology allowed in Part 2). Without a driver mutation: disease progression following at least one line of prior chemotherapy and at least 1 prior anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapy. With a driver mutation must experience disease progression on at least 1 targeted therapeutic agent to be eligible. Detectable prostate-specific membrane antigen (PSMA) expression by PSMA positron emission tomography (PET)/computed tomography (CT) imaging. Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2. Exclusion Criteria: Radiographic evidence of intratumor cavitation, major blood vessel invasion or encasement by cancer. Untreated or symptomatic brain metastases and leptomeningeal disease. History of hemoptysis within 3 months prior to first dose. History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease). Myocardial infarction, unstable angina, cardiac arrhythmias requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months prior to start of dosing. Vasculitis or grade 3/4 gastrointestinal bleeding within 3 months prior to first dose; vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months of first dose. Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to start of dosing. Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with treatment. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). Chronic systemic corticosteroid therapy or any other immunosuppressive therapies unless stopped 7 days prior to first dose. Any biological therapy or immunotherapy within 3 weeks of start of first dose. Major surgery within 4 weeks of first dose. Infection requiring IV antimicrobials for management within 7 days of dosing. Known human immunodeficiency virus (HIV) infection, hepatitis C infection. Active autoimmune disease

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Exploration<br>The dose exploration part of the study will estimate the MTD and/or the RP2D. | Drug: AMG 160<br>* AMG 160 administered as an intravenous (IV) infusion<br>|
| Experimental: Part 2: Dose Expansion - Cohort 1 Non-squamous NSCLC<br>Participants with non-squamous non-small cell lung cancer (NSCLC) will be administered the RP2D identified from the dose exploration part of the study. | Drug: AMG 160<br>* AMG 160 administered as an intravenous (IV) infusion<br>|
| Experimental: Part 2: Dose Expansion - Cohort 2 Squamous NSCLC<br>Participants with squamous NSCLC will be administered the RP2D identified from the dose exploration part of the study. | Drug: AMG 160<br>* AMG 160 administered as an intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience One or More Dose-limiting Toxicities (DLTs) |  | 28 days | 
| Number of Participants who Experience One or More Treatment-emergent Adverse Event (TEAE) |  | Up to 3 years | 
| Number of Participants who Experience One or More Treatment-related Adverse Events |  | Up to 3 years | 
| Number of Participants who Experience Clinically Significant Changes in Vital Signs |  | Up to 3 years | 
| Number of Participants who Experience Clinically Significant Changes in Clinical Laboratory Tests |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) per Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |  | Up to 3 years | 
| Overall Survival |  | Up to 3 years | 
| Progression-free Survival (PFS) |  | Up to 3 years | 
| Time to Response |  | Up to 3 years | 
| Time to Progression |  | Up to 3 years | 
| Duration of Response |  | Up to 3 years | 
| Time to Subsequent Therapy |  | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 160, Phase 1b