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

Stomach Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096666
• Other study ID #: 20120370
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 15, 2014
• Est. completion date: December 7, 2018

Study information

• Verified date: December 2021
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 7, 2018
• Est. primary completion date: November 5, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Stomach Neoplasms

Intervention

Drug:
• AMG 337
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)

Locations

Country	Name	City	State
Japan	Research Site	Kashiwa-shi	Chiba
Japan	Research Site	Kawasaki-shi	Kanagawa
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Suntou-gun	Shizuoka

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1- Adverse events and clinical laboratory abnormalities	Adverse events and clinical laboratory abnormalities defined as DLTs.	17 months
Primary	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	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
Secondary	Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters		17 months
Secondary	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
Secondary	Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2)		17 months
Secondary	Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2)		17 months
Secondary	Phase 2- Progression Free Survival		17 months
Secondary	Phase 2- Overall Survival		17 months
Secondary	Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities		17 months
Secondary	Phase 2- AMG 337 exposure and dose intensity		17 months
Secondary	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
Secondary	Phase 1- Overall Response Rate		17 months
Secondary	Phase 1- Duration of Response		17 months
Secondary	Phase 1- Time to Response		17 months
Secondary	Phase 1- Progression-Free Survival (per RECIST v1.1)		17 months
Secondary	Phase 1- Overall Survival		17 months

External Links

•   AmgenTrials clinical trials website