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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
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)
Research Site
Kashiwa-shi, Chiba, Japan
Research Site
Sapporo, Hokkaido, Japan
Research Site
Kawasaki-shi, Kanagawa, Japan
Research Site
Suntou-gun, Shizuoka, Japan
Phase 1- Adverse events and clinical laboratory abnormalities
Adverse events and clinical laboratory abnormalities defined as DLTs.
Time frame: 17 months
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)
Time frame: 17 months
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).
Time frame: 17 months
Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters
Time frame: 17 months
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)
Time frame: 17 months
Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2)
Time frame: 17 months
Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2)
Time frame: 17 months
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Phase 2- Progression Free Survival
Time frame: 17 months
Phase 2- Overall Survival
Time frame: 17 months
Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities
Time frame: 17 months
Phase 2- AMG 337 exposure and dose intensity
Time frame: 17 months
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.
Time frame: 17 months
Phase 1- Overall Response Rate
Time frame: 17 months
Phase 1- Duration of Response
Time frame: 17 months
Phase 1- Time to Response
Time frame: 17 months
Phase 1- Progression-Free Survival (per RECIST v1.1)
Time frame: 17 months
Phase 1- Overall Survival
Time frame: 17 months