Phase 2 Study of AMG 337 in MET Amplified Gastric/Esophageal Adenocarcinoma or Other Solid Tumors

A Multicenter, Phase 2, Single Arm, Two Cohort Study Evaluating the Efficacy, Safety, and Pharmacokinetics of AMG337 in Subjects With MET Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma or Other MET Amplified Solid Tumors

This is a multi-centre Phase 2 study. The study will evaluate the activity and safety of AMG 337 in patients who have MET amplified gastric, gastroesophageal junction or esophageal adenocarcinoma or other MET amplified solid tumors. The study is designed to estimate the objective response rate of AMG 337 by tumor type.

Study Overview

• Status: Terminated
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: AMG 337

Detailed Description

This is a phase 2, multicenter, single arm, 2 cohort study to assess the safety, efficacy and pharmacokinetics of AMG 337 in MET amplified Gastric/esophageal adenocarcinoma or other solid tumors. Approximately 140 subjects will be enrolled to either Cohort 1 (subjects with MET amplified G/E adenocarcinoma with measurable tumor) or Cohort 2 (subjects with MET amplified solid tumors with measurable tumor/up to 10 subjects with MET amplified G/E adenocarcinoma with non-measurable tumor/up to 10 subjects who have received prior MET antibody therapy). All subjects will self-administer AMG 337 300 mg daily until disease progression or other protocol specified end of treatment criteria is met.

Tumor tissue, biomarkers, Pharmacokinetics and Patient reported Outcomes will all be assessed.

Tumor assessment by RECIST 1.1 will be followed during study treatment.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Research Site
  • Victoria
    • Bentleigh East, Victoria, Australia, 3165
      • Research Site
    • Heidelberg, Victoria, Australia, 3084
      • Research Site
• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
  • Wels, Austria, 4600
    • Research Site
• Belgium
  • Brussels, Belgium, 1000
    • Research Site
  • Bruxelles, Belgium, 1070
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
• Chile
  • Santiago, Chile, 7500921
    • Research Site
  • Santiago, Chile, 8420383
    • Research Site
  • Santiago, Chile, 7630370
    • Research Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Praha 2, Czechia, 120 00
    • Research Site
• France
  • Angers, France, 49933
    • Research Site
  • Bordeaux, France, 33075
    • Research Site
  • Lille Cedex, France, 59020
    • Research Site
  • Lyon cedex 8, France, 69373
    • Research Site
  • Marseille cedex 5, France, 13385
    • Research Site
  • Reims, France, 51092
    • Research Site
  • Saint Herblain, France, 44800
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Köln, Germany, 50937
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • München, Germany, 81675
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 11528
    • Research Site
  • Athens, Greece, 14564
    • Research Site
  • Heraklion - Crete, Greece, 71110
    • Research Site
  • Ioannina, Greece, 45500
    • Research Site
  • Piraeus, Greece, 18537
    • Research Site
• Hungary
  • Budapest, Hungary, 1097
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Kaposvar, Hungary, 7400
    • Research Site
  • Szolnok, Hungary, 5004
    • Research Site
• Italy
  • Ancona, Italy, 60126
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Brescia, Italy, 25123
    • Research Site
  • Cremona, Italy, 26100
    • Research Site
  • Firenze, Italy, 50134
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Milano, Italy, 20162
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Pisa, Italy, 56126
    • Research Site
  • Roma, Italy, 00189
    • Research Site
  • Rozzano MI, Italy, 20089
    • Research Site
  • Torino, Italy, 10126
    • Research Site
  • Udine, Italy, 33100
    • Research Site
• Korea, Republic of
  • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
    • Research Site
  • Hwasun, Korea, Republic of, 519-763
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Research Site
  • Seoul, Korea, Republic of, 138-736
    • Research Site
  • Seoul, Korea, Republic of, 137-701
    • Research Site
  • Seoul, Korea, Republic of, 110-744
    • Research Site
• Peru
  • Lima, Peru, Lima 18
    • Research Site
  • Lima, Peru, LIMA 11
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Elblag, Poland, 82-300
    • Research Site
  • Konin, Poland, 62-500
    • Research Site
  • Lodz, Poland, 93-513
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Russian Federation
  • Krasnodar, Russian Federation, 350040
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 119991
    • Research Site
  • Saint-Petersburg, Russian Federation, 197758
    • Research Site
• Spain
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Andalucía
    • Malaga, Andalucía, Spain, 29010
      • Research Site
    • Sevilla, Andalucía, Spain, 41013
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Northwood, United Kingdom, HA6 2RN
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
    • The Bronx, New York, United States, 10467
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to daily self-administer AMG 337 orally as a whole capsule
• Male or female 18 years of age or over.
• Pathologically confirmed advanced G/GEJ/E adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which subject has received prior therapy for advanced disease, for which no standard therapy exists, or subject refuses standard therapy
• Tumor MET amplified by protocol-specified centralized testing.
• Measurable disease per RECIST 1.1 guidelines. Cohort 2 may include up to 10 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

Exclusion Criteria:

• Known central nervous system metastases
• Candidate for curative surgery or definitive chemoradiation
• Peripheral edema > grade 1
• 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
• Acute Hepatitis B. Chronic Hepatitis B eligible if condition is stable and, in the opinion of the investigator or Amgen physician, if consulted, would not pose a risk to subject safety
• Detectable Hepatitis C virus (indicative of active Hepatitis C)
• 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 inclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; AMG 337 Monotherapy	Drug: AMG 337; AMG 337 300mg orally daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (RECIST v1.1) in subjects with MET Amplified measurable G/GEJ/E adenocarcinoma (Cohort 1)	Determine antitumor activity of AMG 337 in subjects with MET amplified G/GEJ/E adenocarcinoma	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (cohort 1 and subjects with measurable disease at baseline in cohort 2)		2.5 years
Time to response (Cohort 1 and subjects with measurable disease at baseline in cohort 2)		2.5 years
Progression free survival		2.5 years
Overall survival		2.5 years
Incidence and severity of adverse events and significant laboratory abnormalities		2.5 years
AMG 337 exposure and dose intensity		2.5 years
Pharmacokinetic parameters	Including, but not limited to, minimum (trough) concentrations at pre-dose times, maximum concentrations (C max), the time of C max (t max), and area under the plasma concentration - time curve (AUC).	2.5 years
Objective Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2).	Determine antitumor activity of AMG 337 in subjects with other MET amplified solid tumors.	2.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcomes (PRO) Health related quality of life (HRQoL)	To evaluate the impact of AMG 337 on health-related quality of life (HRQoL) in subjects with MET amplified G/GEJ/E adenocarcinoma (Cohort 1 only).	3 years
Tumor tissue and circulating serum biomarkers	assessed at baseline. Circulating tumor cells (CTC) and circulating serum biomarkers will also be assessed at baseline and during study treatment	3 years
Prediction of response rates to AMG 337 by analysing tumor DNA for MET pathway-related genes	To analyse tumor DNA samples for MET pathway-related genes (and other genes based on emerging data) that may predict response to AMG 337	3 years
Response to AMG 337 and MET amplification, expression or presence of mutation in tumor specimens	Explore whether the level of MET amplification, expression, or presence of mutation in tumor specimens correlates with response to AMG 337.	3 years

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 20, 2013

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: MET Amplified Gastric / Gastroesophageal Junction / Esophageal Adenocarcinoma, or other solid tumors.
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma
• Other Study ID Numbers: 20130111; 2013-001277-24 (EudraCT Number)