Stomach Neoplasms
Conditions
Keywords
MET Amplified Gastric / Gastroesophageal Junction / Esophageal Adenocarcinoma, or other solid tumors.
Brief summary
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.
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.
Interventions
DRUGAMG 337
AMG 337 300mg orally daily.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (RECIST v1.1) in subjects with MET Amplified measurable G/GEJ/E adenocarcinoma (Cohort 1) | 2.5 years | Determine antitumor activity of AMG 337 in subjects with MET amplified G/GEJ/E adenocarcinoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free 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 | 2.5 years | 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). |
| Objective Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2). | 2.5 years | Determine antitumor activity of AMG 337 in subjects with other MET amplified solid tumors. |
| 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 | — |
| Overall survival | 2.5 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Prediction of response rates to AMG 337 by analysing tumor DNA for MET pathway-related genes | 3 years | To analyse tumor DNA samples for MET pathway-related genes (and other genes based on emerging data) that may predict response to AMG 337 |
| Response to AMG 337 and MET amplification, expression or presence of mutation in tumor specimens | 3 years | Explore whether the level of MET amplification, expression, or presence of mutation in tumor specimens correlates with response to AMG 337. |
| Patient Reported Outcomes (PRO) Health related quality of life (HRQoL) | 3 years | 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). |
| Tumor tissue and circulating serum biomarkers | 3 years | assessed at baseline. Circulating tumor cells (CTC) and circulating serum biomarkers will also be assessed at baseline and during study treatment |
Countries
Australia, Austria, Belgium, Canada, Chile, Czechia, France, Germany, Greece, Hungary, Italy, Peru, Poland, Russia, South Korea, Spain, United Kingdom, United States
Outcome results
None listed