AMG 337 for the Treatment of Gastric, Esophageal and Gastroesophageal Junction Cancers, and Other Solid Tumors

Phase 1

• Conditions: MedDRA version: 14.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10030137Term: Oesophageal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MET Amplified Gastric (G), Gastroesophageal Junction (GEJ), or Esophageal (E) Adenocarcinoma or Other MET Amplified Solid Tumors; MedDRA version: 14.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001277-24-IT
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-12
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

General
- Subjects have provided informed consent/assent prior to initiation of any study-specific activities/procedures or subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of
the investigator, may compromise the ability of the subject to give written informed consent.
- Subjects have agreed to and are able to daily self-administer AMG 337 orally as a whole capsule

Demographic
- Male or female subjects = 18 years of age at the time of enrollment

Disease-related
- Subjects must have a pathologically confirmed advanced G/GEJ/E
adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which the subject has 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. Testing may be performed by central laboratory prior to main study informed consent if subject signs a separate consent for the purposes of tumor tissue testing
- Availability of recent (preferred) or archival tumor tissue
- 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
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Laboratory
- Adequate organ function as evidenced by the following laboratory studies within 28 days prior to enrollment:
? Hemoglobin = 9 g/dL
? Absolute neutrophil count = 1.5 x 109/L
? Platelet conut = 100 x 109/L
? Creatinine clearanc=e 50 mL/minute (calculated or measured)
? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x upper limit of normal (ULN) or AST and ALT = 5.0 x ULN if liver metastases are present
? Total bilirubin (TBL) = 1.5 x ULN
? International normalized ratio (INR) = ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 84
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

- Known central nervous system metastases. Subject is a candidate for curative surgery or definitive chemoradiation. Peripheral edema > grade 1.
Currently receiving any anti-tumor treatments, or less than 14 days prior to enrollment since ending anti-tumor treatment.
- Therapeutic or palliative radiation therapy less than 14 days prior to study day 1 or still experiencing toxicities from radiation therapy or radiation therapy administered to the only site of
disease.
- Use of a strong CYP3A4 inhibitor less than 14 days prior to study day 1.
- Ingestion of grapefruit or grapefruit products and other foods that are known to inhibit CYP3A4 less than 7 days prior to study day 1.
- Use of strong CYP3A4 inducers less than 14 days prior to study day 1.
- Use of St. John’s Wort and other herbal supplements known to induce CYP3A4 less than 14 days prior to study day 1.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine antitumor activity of AMG 337 in subjects with MET amplified G/GEJ/E adenocarcinoma.;Secondary Objective: To determine the antitumor activity of AMG 337 in subjects with other MET amplified solid tumors. Evaluate the safety and pharmacokinetics (PK) of AMG 337.;Primary end point(s): Objective response rate (ORR, per RECIST v1.1) in subjects with MET amplified measurable G/GEJ/E adenocarcinoma (Cohort 1);Timepoint(s) of evaluation of this end point: Tumour assessment scans will be taken at screening, week 8 (± 3 days), and then every 8 weeks (Q8W) (± 7 days) during study treatment until week 32, independent of treatment cycle. From week 32 onward, tumour assessment scans will be taken every 12<br>weeks (Q12W) (± 7 days) during study treatment, independent of treatment cycle.