MET Amplified Gastric (G), Gastroesophageal Junction (GEJ), or Esophageal (E) Adenocarcinoma or Other MET Amplified Solid Tumors MedDRA version: 14.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified
Conditions
Interventions
Product Name: AMG 337
Product Code: AMG 337
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: AMG 337
Current Sponsor code: AMG 337 hydrate
Concentration unit: mg milligram(s)
Concentration type
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 weeks (Q12W) (± 7 days) during study treatment, independent of treatment cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ORR (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in Cohort 2) - DOR (duration of response) (Cohort 1 and subjects with measurable disease at baseline in Cohort 2) - Time to response (TTR) (Cohort 1 and subjects with measurable disease at baseline in Cohort 2) - Progression-free survival (PFS) - Overall survival (OS) - Incidence and severity of adverse events and significant laboratory abnormalities - AMG 337 exposure and dose intensity - Pharmacokinetic parameters including, but not limited to, minimum (trough) concentrations at pre-dose times, maximum concentration (Cmax), the time of Cmax (tmax), and area under the plasma concentration – time curve (AUC);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 weeks (Q12W) (± 7 days) during study treatment, independent of treatment cycle. Patient-reported outcomes assessment will be done at baseline and at every radiological assessment thereafter, including radiological assessments to confirm tumour progression when symptoms of disease progression occur. CTC and circulating serum biomarkers will also be assessed at baseline and during study treatment. | — |
Countries
Australia, Austria, Belgium, Canada, Chile, Czech Republic, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Peru, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed