Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.1 Level: LLT Classification code 10084227 Term: Gastroesophageal junction cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Part 1: - Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 - Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) - Participant must be a candidate to receive mFOLFOX6 and nivolumab - Adequate organ function as follows: Absolute neutrophil count = 1.5 x 10^9/L Platelet count = 100 x 10^9/L Hemoglobin = 9 g/dl Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) =65 years) yes F.1.3.1 Number of subjects for this age range 162
Exclusion criteria
Exclusion criteria: - Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway - Known positive human epidermal growth factor receptor 2 (HER2) status - Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease - Peripheral sensory neuropathy grade 2 or higher - Clinically significant cardiac disease - Other malignancy within the last 2 years (exceptions for definitively treated disease) - Chronic or systemic ophthalmologic disorders - Major surgery or other investigational study within 28 days prior to randomization - Palliative radiotherapy within 14 days prior to randomization - Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer - Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study Please refer to protocol for remaining exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b – Safety Lead-In •To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 and nivolumab Phase 3 •To compare efficacy of bemarituzumab plus mFOLFOX6 and nivolumab to placebo plus mFOLFOX6 and nivolumab asassessed by overall survival;Secondary Objective: Phase 1b – Safety Lead-In •To evaluate preliminary anti-tumor activity of bemarituzumab plus mFOLFOX6 and nivolumab •To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with mFOLFOX6 and nivolumab •To characterize the immunogenicity of bemarituzumab Phase 3 •To compare efficacy between the treatment arms as assessed by: -Progression free survival (PFS) -Objective response (OR) •To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 and nivolumab compared to placbo plus mFOLFOX6 and nivolumab •To compare efficacy between the treatment arms as assessed by: -Duration of response (DOR) -Disease control •To assess subject-reported and quality of life (QoL) outcomes •To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with mFOLFOX6 and nivolumab •To characterize the immunogenicity of bemarituzumab;Primary end point(s): Phase 1b – Safety Lead-In •Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, electrocardiogram (ECG), physical examinations, and clinical laboratory tests Phase 3 •Overall survival, defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive;Timepoint(s) of evaluation of this end point: Safety: throughout Phase 1b of the study OS: every 3 months (± 1 month) after the safety follow-up visit until 443 total deaths have been observed in the study or 15 months after the last subject is enrolled (whichever occurs later) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b – Safety Lead-In •Objective response •Duration of response •Disease control (DCR) •Progression free survival (PFS) •Overall survival (OS) •PK parameters for bemarituzumab •Anti-bemarituzumab antibody formation Phase 3 •PFS •Objective response •Treatment-emergent adverse events (including all adverse events, grade = 3, serious adverse events, fatal adverse events, and adverse events requiring permanent discontinuation of investigational product) •Clinically significant changes in vital signs, visual acuity, and clinical laboratory tests •Duration of response •Disease control •Subjective score and change from baseline in following assessments: - EORTC Quality of Life Questionnaire Version 3.0(QLQ-C30) individual scores (raw and transformed) for the 5 functional scales, 9 symptom scales, global health status/quality of life scale and change from baseline at each assessment - Stomach cancer related symptoms measured by EORTC-QLQ-STO22 - Summary scores at each assessment and changes from baseline of visual analogue scale (VAS) scores as measured by EuroQol 5-dimensional (EQ-5D-5L) - Time to deterioration in stomach-cancer related symptoms scores - Time to deterioration in health-related quality of life (HRQoL) scores - Time to deterioration in physical function scores •PK parameters for bemarituzumab •Anti-bemarituzumab antibody formation;Timepoint(s) of evaluation of this end point: PFS, ORR, DOR: Radiological/tumor assessment: Every 8 weeks until week 56 after cycle 1 day 1, then every 12 weeks; until start of new anticancer therapy, disease progression, death, withdrawal of consent, or end of study, whichever occurs first. TAEs: throughout study For other endpoints see Schedule of Activity (SoA) | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Portugal, Romania, Russian Federation, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen S.A.
Outcome results
None listed