A Study Evaluating Bemarituzumab in Combination With Other Anti-cancer Therapies in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer.

Study Overview
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Brief Summary
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The main objectives of this study are to evaluate the safety and tolerability of bemarituzumab in combination with other anti-cancer therapies, and to evaluate the efficacy of bemarituzumab in combination with S-1 and oxaliplatin (SOX) and nivolumab as assessed by objective response.

Official Title
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A Phase 1b/2 Study Evaluating the Safety, Tolerability, Efficacy, and Pharmacokinetics of Bemarituzumab in Combination With Other Anti-cancer Therapies in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer (FORTITUDE-103).

Conditions
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Gastric Cancer, Gastroesophageal Junction Cancer

Intervention / Treatment
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* Drug: Bemarituzumab
* Drug: CAPOX
* Drug: SOX
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amendable to curative therapy. Ability to provide tumor sample, either archival (obtained within 6 months to joining study) or fresh biopsy. For certain arms for Part 1, FGFR2b overexpression positive defined as any FGFR2b 2+/3+ TC determined by centrally performed immunohistochemistry (IHC), based on tumor sample provided. For Part 2, FGFR2b overexpression positive defined as FGFR2b ≥10% 2+/3+ TC determined by centrally performed IHC testing, based on tumor sample provided. Easter Cooperative Oncology Group (ECOG) performance score less than or equal to 1. Measurable or non-measurable disease as long as evaluable by Response Evaluation Criteria Solid Tumors (RECIST) version 1.1 Participant has no contradictions to CAPOX/SOX plus or minus nivolumab. Adequate organ function. For Part 2, measurable disease according to RECIST v1.1. Exclusion Criteria: Prior treatment for metastatic or unresectable disease (Note: prior adjuvant or neo-adjuvant therapy for local disease is allowed if ended more than 6 months of 1st dose). Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway. Known human epidermal growth factor receptor 2 (HER2) positive Untreated or symptomatic central nervous system (CNS) disease or brain metastases. Peripheral sensory neuropathy greater than or equal to Grade 2. Clinically significant cardiac disease. Other malignancy within the last 2 years (exceptions for definitively treated disease). Chronic or systemic ophthalmological disorders. Major surgery or other investigational study within 28 days of first study treatment dose. Palliative radiotherapy within 14 days of first study treatment dose. Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer. History or evidence of systemic disease or ophthalmological disorders requiring chronic use of ophthalmic corticosteroids.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort A: Bemarituzumab with CAPOX<br> | Drug: Bemarituzumab<br>* Intravenous (IV) infusion<br>Drug: CAPOX<br>* CAPOX administered as a combination of oxaliplatin as an IV infusion and capecitabine orally as tablets.<br>|
| Experimental: Part 1 Cohort C: Bemarituzumab with CAPOX and Nivolumab<br> | Drug: Bemarituzumab<br>* Intravenous (IV) infusion<br>Drug: CAPOX<br>* CAPOX administered as a combination of oxaliplatin as an IV infusion and capecitabine orally as tablets.<br>Drug: Nivolumab<br>* IV infusion.<br>|
| Experimental: Part 1 Cohort D: Bemarituzumab with SOX and Nivolumab<br> | Drug: Bemarituzumab<br>* Intravenous (IV) infusion<br>Drug: SOX<br>* SOX administered as a combination of oxaliplatin as an IV infusion and S-1 orally.<br>Drug: Nivolumab<br>* IV infusion.<br>|
| Experimental: Part 2: Bemarituzumab with SOX and Nivolumab.<br> | Drug: Bemarituzumab<br>* Intravenous (IV) infusion<br>Drug: SOX<br>* SOX administered as a combination of oxaliplatin as an IV infusion and S-1 orally.<br>Drug: Nivolumab<br>* IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) |  | Day 1 up to Day 21 | 
| Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) |  | Day 1 to end of treatment (up to approximately 1 year) | 
| Part 2: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |  | Up to 30 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Area Under the Concentration-time Curve (AUC) of Bemarituzumab |  | Day 1 to end of treatment (up to approximately 1 year) | 
| Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab |  | Day 1 to end of treatment (up to approximately 1 year)) | 
| Part 1: Observed Concentration at the end of a Dose Interval (Ctrough) of Bemarituzumab |  | Day 1 to end of treatment (up to approximately 1 year) | 
| Part 1: OR per RECIST v1.1 |  | Up to 2 years | 
| Part 1: Duration of Response (DoR) per RECIST v1.1 |  | Up to 2 years | 
| Part 1: Disease Control Rate (DCR) |  | Up to 2 years | 
| Part 1: Progression-free Survival (PFS) per RECIST v1.1 |  | Up to 2 years | 
| Part 1: Overall Survival (OS) |  | Up to 2 years | 
| Part 2: Number of Participants Who Experience TEAEs |  | Up to 30 months | 
| Part 2: DoR per RECIST v1.1 |  | Up to 30 months | 
| Part 2: Time to Response (TTR) per RECIST v1.1 |  | Up to 30 months | 
| Part 2: Disease Control (DC) per RECIST v1.1 |  | Up to 30 months | 
| Part 2: PFS per RECIST v1.1 |  | Up to 30 months | 
| Part 2: OS |  | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Gastroesophageal Junction Cancer, Bemarituzumab, FGFR2b Overexpression