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

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

Sponsors

Lead sponsor: Amgen

Source 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.

Overall Status Completed
Start Date April 15, 2014
Completion Date December 7, 2018
Primary Completion Date November 5, 2015
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Phase 1- Adverse events and clinical laboratory abnormalities 17 months
Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with MET amplified measurable gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1) 17 months
Secondary Outcome
Measure Time Frame
Phase 1- Pharmacokinetic parameters 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) 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 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
Enrollment 11
Condition
Intervention

Intervention type: Drug

Intervention name: AMG 337

Description: 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)

Arm group label: Single arm

Eligibility

Criteria:

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.

Gender: All

Minimum age: 20 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
MD Study Director Amgen
Location
facility
Research Site | Kashiwa-shi, Chiba, 277-8577, Japan
Research Site | Sapporo-shi, Hokkaido, 060-8648, Japan
Research Site | Kawasaki-shi, Kanagawa, 216-8511, Japan
Research Site | Suntou-gun, Shizuoka, 411-8777, Japan
Location Countries

Japan

Verification Date

December 2018

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Single arm

Arm group type: Experimental

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov