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

Phase 1

Completed

• Conditions: Stomach Neoplasms
• Interventions: Drug: AMG 337

• Registration Number: NCT02096666
• Lead Sponsor: Amgen

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-03-24
• Study First Submitted QC: 2014-03-24
• Study First Posted: 2014-03-26
• Study Start: 2014-04-15
• Primary Completion: 2015-11-05
• Disposition First Submitted: 2016-03-28
• Disposition First Submitted QC: 2016-03-28
• Disposition First Posted: 2016-04-29
• Study Completion: 2018-12-07
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-23
• Last Update Posted: 2021-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	AMG 337	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2)	17 months	Determine anti-tumor activity in AMG 337 in subjects with MET amplified solid tumors (subjects with measurable disease in cohort 2)
Phase 1- Duration of Response	17 months
Phase 1- Progression-Free Survival (per RECIST v1.1)	17 months
Phase 1- Pharmacokinetic parameters	17 months	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).
Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2)	17 months
Phase 2- AMG 337 exposure and dose intensity	17 months
Phase 1- Overall Survival	17 months
Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters	17 months
Phase 2- Overall Survival	17 months
Phase 1- Time to Response	17 months
Phase 2- Progression Free Survival	17 months
Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities	17 months
Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2)	17 months
Phase 2- Pharmacokinetic parameters	17 months	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.
Phase 1- Overall Response Rate	17 months

Trial Locations

Locations (1)

Research Site; 🇯🇵 Suntou-gun, Shizuoka, Japan