Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
Conditions
Interventions
Experimental: Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab
Participants will be administered bemarituzumab at different doses with mFOLFOX6and nivolumab to determine the recommende
Sponsors
Kaneda Hirokazu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Part 1 and Part 2: 1. Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 3. Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) 4. Participant has no contraindications to nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Participants in Part 1 must have no contraindications to mFOLFOX6. Participants in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Participants in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist 5. 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 without red blood cell (RBC)transfusion within 7 days prior to the first dose of study treatment - Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) = 50 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age] x Mass [kg]/[72 x Creatinine mg/dL]) (x 0.85 if female). - Part 2 only: Calculated or measured creatinine clearance (CrCl) of >= 30 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age] x Mass [kg]/[72 x Creatinine mg/dL]) (x 0.85 if female). - INR or prothrombin time (PT) = 10% 2+/3+ tumor cells (TC) as determined by centrally performed immunohistochemistry (IHC) testing, based on tumor sample either archival (obtained within 6 months/180 days prior to signing pre-screening informed consent) or a fresh biopsy.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway 2. Known positive human epidermal growth factor receptor 2 (HER2) status 3. Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease 4. Peripheral sensory neuropathy grade 2 or higher 5. Clinically significant cardiac disease 6.Other malignancy within the last 2 years (exceptions for definitively treated disease) 7. Chronic or systemic ophthalmologic disorders 8. Major surgery or other investigational study within 28 days prior to randomization 9. Palliative radiotherapy within 14 days prior to randomization 10. Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer 11. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part 1: Number of Participants Who Experienced DLTs [Time Frame: 28 days] 2. Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Up to 4.5 years] 3. Part 1: Number of Participants Who Experienced One or More Related TEAEs [Time Frame: Up to 4.5 years] 4. Part 1: Number of Participants With Clinically Significant Changes in Vital Signs [Time Frame: Up to 4.5 years] 5. Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity [Time Frame: Up to 4.5 years] 6. Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations [Time Frame: Up to 4.5 years] 7. Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Time Frame: Up to 4.5 years] 8. Part 2: Overall Survival in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part 1: Objective Response (OR) [Time Frame: Up to 4.5 years] 2. Part 1: Duration of Response (DoR) [Time Frame: Up to 4.5 years] 3. Part 1: Disease Control Rate (DCR) [Time Frame: Up to 4.5 years] 4. Part 1: Progression Free Survival (PFS) [Time Frame: Up to 4.5 years] 5. Part 1: Overall Survival [Time Frame: Up to 4.5 years] 6. Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years] 7. Part 1: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years] 8. Part 1: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years] 9. Part 1: Number of Participants With Anti-Bemarituzumab Antibody Formation [Time Frame: Day 1 to up to 4.5 years] 10. Part 2: PFS in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years] 11. Part 2: OR in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years] 12. Part 2: Number of Participants Who Experienced One or More TEAEs [Time Frame: Up to 4.5 years] 13. Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [Time Frame: Up to 4.5 years] 14. Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [Time Frame: Up to 4.5 years] 15. Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Time Frame: Up to 4.5 years] 16. Part 2: Overall Survival in All Randomized Participants [Time Frame: Up to 4.5 years] 17. Part 2: PFS in All Randomized Participants [Time Frame: Up to 4.5 years] 18. Part 2: Objective Response Rate (ORR) in All Randomized Participants [Time Frame: Up to 4.5 years] 19. Part 2: DoR in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years] 20. Part 2: DCR in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years] 21. Part 2: Mean Score in European Organization for Research and | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Poland, Portugal, Romania, Singapore, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed