Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression

Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to compare efficacy of bemarituzumab combined with oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX6) to placebo plus mFOLFOX6 as assessed by overall survival (OS) in participants with FGFR2b ≥10% 2+/3+ tumor cell staining (FGFR2b ≥10% 2+/3+TC)

Official Title
-----------------
A Randomized, Multi-center, Double-blind, Placebo-controlled Phase 3 Study of Bemarituzumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer With FGFR2b Overexpression

Conditions
-----------------
Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: Bemarituzumab
* Drug: mFOLFOX6
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults with histologically documented unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy Fibroblast growth factor receptor 2b (FGFR2b) ≥10% 2+/3+ tumor cell staining 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 Eastern Cooperative Oncology Group (ECOG) less than or equal to 1 Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) V 1.1 Participant has no contraindications to mFOLFOX6 chemotherapy Adequate organ and bone marrow function: absolute neutrophil count greater than or equal to 1.5 times 10^9/L platelet count greater than or equal to 100 times 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 aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times the upper limit of normal (ULN) (or less than 5 times ULN if liver involvement). Total bilirubin less than 1.5 times ULN (or less than 2 times ULN if liver involvement); with the exception of participants with Gilbert's disease) calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age]) × Mass [kg]/[72 × Creatinine mg/dL]) (x 0.85 if female) international normalized ratio (INR) or prothrombin time (PT) less than 1.5 times ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment Exclusion Criteria: Prior treatment for metastatic or unresectable disease (Note: prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed if completed more than 6 months prior to first dose of study treatment) 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 prior to first dose of study treatment Palliative radiotherapy within 14 days prior to the first dose of study treatment Evidence of or recent history (within 6 months) of corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bemarituzumab with mFOLFOX6<br> | Drug: Bemarituzumab<br>* Intravenous (IV) infusion<br>Drug: mFOLFOX6<br>* mFOLFOX6 administered as a combination of oxaliplatin and leucovorin as IV infusions. 5-FU administered as bolus followed by additional administration as IV infusion.<br>|
| Active Comparator: Placebo with mFOLFOX6<br> | Drug: mFOLFOX6<br>* mFOLFOX6 administered as a combination of oxaliplatin and leucovorin as IV infusions. 5-FU administered as bolus followed by additional administration as IV infusion.<br>Drug: Placebo<br>* IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Objective Response Rate (ORR) | ORR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE) | Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests after first dose will be recorded as TEAEs. | Up to approximately 3.5 years | 
| Overall Survival | Overall survival in all randomized participants | Up to approximately 3.5 years | 
| Progression-free Survival (PFS) | PFS in all randomized participants | Up to approximately 3.5 years | 
| Objective Response Rate (ORR) | ORR in all randomized participants | Up to approximately 3.5 years | 
| Duration of Response (DOR) | DOR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Disease Control Rate | Disease Control Rate in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Mean Subjective Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Baseline up to approximately 3.5 years | 
| Stomach Cancer Related Symptom Mean Subjective Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Change from Baseline in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Baseline up to approximately 3.5 years | 
| Mean Subjective Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Change from Baseline of Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Baseline up to approximately 3.5 years | 
| Time to Deterioration in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Up to approximately 3.5 years | 
| Time to Deterioration in Physical Function Score as Measured by a Subscale of European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) | Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants | Day 1 up to approximately 3.5 years | 
| Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma |  | Day 1 up to approximately 3.5 years | 
| Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab in Combination with mFOLFOX6 in Plasma |  | Day 1 up to approximately 3.5 years | 
| Number of Participants with an Anti-bemarituzumab Antibody Formation |  | Day 1 up to approximately 3.5 years | 

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