A Phase 1/2 Study Evaluating AMG 337 in Asian Subjects

Study Overview
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Brief Summary
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This is a multicenter, Phase 1/2 study. The study will evaluate the tolerability, safety and activity of AMG 337 in Asian subjects who have advanced solid tumors (Phase 1) or subjects with MET amplified tumors with a focus on gastric/gastroesophageal junction/esophageal adenocarcinoma (Phase 2).

Detailed Description
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This is a Phase 1/2, multicenter, single arm, open-label study to assess the safety, efficacy and pharmacokinetics of AMG 337 in solid tumors. In the Phase 1, approximately 3 to 45 subjects enrolled in a 3+3+3 dose escalation scheme evaluating two dose levels. In the Phase 2, approximately 140 subjects will be enrolled to either Cohort 1 (subjects with MET amplified /gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma with measurable tumor) or Cohort 2 (subjects with MET amplified solid tumors with measurable tumor and subjects with MET amplified G/GEJ/E adenocarcinoma with non-measurable tumor). All subjects will self-administer AMG 337 daily until disease progression or other protocol specified end of treatment criteria are met. Tumor assessment by RECIST 1.1 will be followed during study treatment. Tumor tissue, biomarkers, pharmacokinetics and Patient Reported Outcomes will be assessed.

Official Title
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A Multicenter, Phase 1/2, Open-Label Study Evaluating the Tolerability, Safety, Pharmacokinetics, and Efficacy of AMG 337 in Asian Subjects

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: AMG 337


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to self administer daily AMG 337 as a whole capsule Male or female 20 years of age or over Phase 1: Subjects must have a pathologically confirmed, advanced solid tumor for which the subjects have received prior therapy for advanced disease, for which no standard therapy exists, or the subject refuses standard therapy. Phase 2: Subjects must have a pathologically confirmed, advanced G/GEJ/E adenocarcinoma (cohort 1) or other solid tumor (cohort 2) for which the subjects have received prior therapy for advanced disease, or for which no standard therapy exists, or the subject refuses standard therapy. Tumor MET amplified by protocol-specified centralized testing (phase 2 only). Phase 1: Measurable or non-measurable disease per RECIST v1.1 Phase 2: Measurable disease per RECIST v1.1 guidelines. Cohort 2 may include subjects with advanced MET amplified G/GEJ/E adenocarcinoma with non-measurable tumor per RECIST v1.1. (ECOG) Performance Status of 0, 1, or 2 Other protocol defined inclusion criteria may apply. Exclusion Criteria: Known central nervous system metastases. Subject is a candidate for curative surgery or definitive chemoradiation. Peripheral edema > grade 1. Subjects who have persistent gastric outlet obstruction, complete dysphagia or are dependent upon jejunostomy for feeding. Significant gastrointestinal disorder(s) that in the opinion of the Investigator may influence drug absorption. Currently receiving any anti-tumor treatments, or less than 14 days prior to enrollment since ending anti-tumor treatment. Prior treatment with small molecule inhibitors of the MET pathway. Other protocol defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br> | Drug: AMG 337<br>* Phase 1- AMG 337 150 mg, 200mg and 300 mg orally daily. Additional 150 mg and 200 mg orally twice daily. Phase 2- AMG 337 (dose determined by Phase 1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1- Adverse events and clinical laboratory abnormalities | Adverse events and clinical laboratory abnormalities defined as DLTs. | 17 months | 
| Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with MET amplified measurable gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1) | Determine anti-tumor activity of AMG 337 in subjects with MET amplified gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1) | 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1- Pharmacokinetic parameters | Including, but not limited to, minimum (trough) concentrations, maximum concentrations (C max), the time of C max (t max), and area under the plasma concentration- time curve (AUC). | 17 months | 
| Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters |  | 17 months | 
| Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2) | Determine anti-tumor activity in AMG 337 in subjects with MET amplified solid tumors (subjects with measurable disease in cohort 2) | 17 months | 
| Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2) |  | 17 months | 
| Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2) |  | 17 months | 
| Phase 2- Progression Free Survival |  | 17 months | 
| Phase 2- Overall Survival |  | 17 months | 
| Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities |  | 17 months | 
| Phase 2- AMG 337 exposure and dose intensity |  | 17 months | 
| Phase 2- Pharmacokinetic parameters | Including, but not limited to, minimum (trough) concentrations at pre-dose times and maximum concentrations (C max), the time of C max (t max), and area under the plasma concentration- time curve (AUC) for intensive pharmacokinetic sampling. | 17 months | 
| Phase 1- Overall Response Rate |  | 17 months | 
| Phase 1- Duration of Response |  | 17 months | 
| Phase 1- Time to Response |  | 17 months | 
| Phase 1- Progression-Free Survival (per RECIST v1.1) |  | 17 months | 
| Phase 1- Overall Survival |  | 17 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MET Amplified Gastric/ Gastroesophageal Junction/ Esophageal Adenocarcinomas, or other solid tumors