Clinical trial NCT02096666: A Phase 1/2 Study Evaluating AMG 337 in Asian Subjects
Official title: A Multicenter, Phase 1/2, Open-Label Study Evaluating the Tolerability, Safety, Pharmacokinetics, and Efficacy of AMG 337 in Asian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stomach Neoplasms
Keywords: MET Amplified Gastric/ Gastroesophageal Junction/ Esophageal Adenocarcinomas, or other solid tumors
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-03-26
Enrollment: 11
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 1- Adverse events and clinical laboratory abnormalities
timeFrame: 17 months
measure: Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with MET amplified measurable gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1)
timeFrame: 17 months
Secondary outcomes:
measure: Phase 1- Pharmacokinetic parameters
timeFrame: 17 months
measure: Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters
timeFrame: 17 months
measure: Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2)
timeFrame: 17 months
measure: Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2)
timeFrame: 17 months
measure: Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2)
timeFrame: 17 months
measure: Phase 2- Progression Free Survival
timeFrame: 17 months
measure: Phase 2- Overall Survival
timeFrame: 17 months
measure: Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities
timeFrame: 17 months
measure: Phase 2- AMG 337 exposure and dose intensity
timeFrame: 17 months
measure: Phase 2- Pharmacokinetic parameters
timeFrame: 17 months
measure: Phase 1- Overall Response Rate
timeFrame: 17 months
measure: Phase 1- Duration of Response
timeFrame: 17 months
measure: Phase 1- Time to Response
timeFrame: 17 months
measure: Phase 1- Progression-Free Survival (per RECIST v1.1)
timeFrame: 17 months
measure: Phase 1- Overall Survival
timeFrame: 17 months
Other outcomes:
Locations:
city: Kashiwa-shi
country: Japan
facility: Research Site
state: Chiba
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Kawasaki-shi
country: Japan
facility: Research Site
state: Kanagawa
city: Suntou-gun
country: Japan
facility: Research Site
state: Shizuoka
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Yasui H, Go N, Yang H, Amore BM, Jung AS, Doi T. A Phase 1 study evaluating AMG 337 in Asian patients with advanced solid tumors. Jpn J Clin Oncol. 2017 Aug 1;47(8):772-776. doi: 10.1093/jjco/hyx067.