Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer
- Conditions
- Gastric Cancer , Gastroesophageal Junction Adenocarcinoma
- Registration Number
- JPRN-jRCT2031210669
- Lead Sponsor
- Kaneda Hirokazu
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 528
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 mFOLFOX6 chemotherapy or nivolumab
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) <3 x upper limit of normal (ULN) (or < 5 x ULN if liver involvement).
- Total bilirubin <1.5 x ULN (or < 2 x ULN if liver involvement or Gilbert's disease)
- Calculated or measured creatinine clearance (CrCl) of >= 50 mL/minute calculated using the formula of Cockcroft and Gault
- International Normalized Ratio (INR) or prothrombin time (PT) < 1.5 x ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment.
Additional Inclusion Criteria Part 2:
6. No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab. Prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment.
7. Fibroblast growth factor receptor 2b (FGFR2b) >= 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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Part 1: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [ Time Frame: 28 days ]<br>2. Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]<br>3. Part 1: Number of Participants Who Experienced One or More Related TEAEs [ Time Frame: Up to 4.5 years ]<br>4. Part 1: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]<br>5. Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]<br>6. Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations [ Time Frame: Up to 4.5 years ]<br>7. Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]<br>8. Part 2: Overall Survival in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
- Secondary Outcome Measures
Name Time Method