Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer.
Phase 3
Active, not recruiting
- Conditions
- Gastric CancerGastroesophageal Junction Adenocarcinoma
- Interventions
- Registration Number
- NCT05111626
- Lead Sponsor
- Amgen
- Brief Summary
The main objective of Part 1 is to evaluate the safety and tolerability of bemarituzumab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) and nivolumab.
The main objective Part 2 is to compare efficacy of bemarituzumab plus chemotherapy (mFOLFOX6 or capecitabine combined with oxaliplatin (CAPOX)) and nivolumab to placebo plus chemotherapy (mFOLFOX6 or CAPOX) and nivolumab as assessed by overall survival.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 515
Inclusion Criteria
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab Bemarituzumab Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK). Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab Nivolumab Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK). Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab Chemotherapy Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK). Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Bemarituzumab Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle. Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Nivolumab Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle. Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Chemotherapy Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle. Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Nivolumab Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle. Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Chemotherapy Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle. Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Placebo Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants Who Experienced DLTs 28 days Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) Up to 4.5 years Part 1: Number of Participants Who Experienced One or More Related TEAEs Up to 4.5 years Part 1: Number of Participants With Clinically Significant Changes in Vital Signs Up to 4.5 years Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity Up to 4.5 years Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations Up to 4.5 years Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests Up to 4.5 years Part 2: Overall Survival in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Up to 4.5 years
- Secondary Outcome Measures
Name Time Method Part 1: Duration of Response (DoR) Up to 4.5 years Part 1: Disease Control Rate (DCR) Up to 4.5 years Part 1: Progression Free Survival (PFS) Up to 4.5 years Part 1: Overall Survival Up to 4.5 years Part 1: Area Under the Concentration Time Curve (AUC) of Bemarituzumab Day 1 to up to 4.5 years Part 2: Cmax of Bemarituzumab Day 1 to up to 4.5 years Part 1: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab Day 1 to up to 4.5 years Part 1: Number of Participants With Anti-Bemarituzumab Antibody Formation Day 1 to up to 4.5 years Part 2: PFS in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Up to 4.5 years Part 2: Overall Survival in All Randomized Participants Up to 4.5 years Part 2: PFS in All Randomized Participants Up to 4.5 years Part 2: Number of Participants Who Experienced One or More TEAEs Up to 4.5 years Part 2: Number of Participants With Clinically Significant Changes in Vital Signs Up to 4.5 years Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity Up to 4.5 years Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests Up to 4.5 years Part 2: OR Up to 4.5 years Part 2: DoR Up to 4.5 years Part 2: DCR Up to 4.5 years Part 2: Mean Score in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Version 3.0 (QLQ-C30) Individual Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Up to 4.5 years Part 2: Change From Baseline in EORTC QLQ-C30 Individual Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Baseline to up to 4.5 years Part 2: Mean Score in Stomach Cancer Related Symptoms Measured by EORTC Quality of Life Questionnaire-Stomach 22 (QLQ-STO22) in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Up to 4.5 years Part 2: Change From Baseline in Stomach Cancer Related Symptoms Measured by EORTC QLQ-STO22 in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Baseline to up to 4.5 years Part 2: Mean Score of Visual Analogue Scale (VAS) Scores as Measured by EuroQol 5-dimensional (EQ-5D-5L) in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Up to 4.5 years Part 2: Change From Baseline of VAS Scores as Measured by EQ-5D-5L in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Baseline to up to 4.5 years Part 2: Time to Deterioration in Stomach Cancer Related Symptoms Measured by EORTC QLQ-STO22 in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Day 1 to up to 4.5 years Part 2: Time to Deterioration in Health-Related Quality of Life (HRQoL) Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Day 1 to up to 4.5 years Part 2: Time to Deterioration in Physical Function Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants Day 1 to up to 4.5 years Part 2: AUC of Bemarituzumab Day 1 to up to 4.5 years Part 2: Ctrough of Bemarituzumab Day 1 to up to 4.5 years Part 2: Number of Participants With Anti-Bemarituzumab Antibody Formation Day 1 to up to 4.5 years Part 1: Objective Response (OR) Up to 4.5 years Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab Day 1 to up to 4.5 years
Trial Locations
- Locations (347)
Mayo Clinic - Arizona
🇺🇸Phoenix, Arizona, United States
The Oncology Institute Clinical Research
🇺🇸Cerritos, California, United States
Cancer and Blood Specialty Clinic
🇺🇸Downey, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of California Irvine
🇺🇸Orange, California, United States
Torrance Memorial Physician Network
🇺🇸Redondo Beach, California, United States
Translational Research in Oncology - US Inc
🇺🇸Santa Monica, California, United States
Translational Research in Oncology US Inc, Trio Central Pharmacy
🇺🇸Santa Monica, California, United States
Olive View-University of California in Los Angeles Medical Center
🇺🇸Sylmar, California, United States
Scroll for more (337 remaining)Mayo Clinic - Arizona🇺🇸Phoenix, Arizona, United States