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

Phase 3

Active, not recruiting

• Conditions: Gastric Cancer; Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: Bemarituzumab; Drug: mFOLFOX6; Drug: Placebo

• Registration Number: NCT05052801
• Lead Sponsor: Amgen

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-13
• Study First Submitted QC: 2021-09-13
• Study First Posted: 2021-09-22
• Study Start: 2022-03-07
• Primary Completion: 2025-06-20
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-18
• Last Update Posted: 2025-07-23
• Study Completion: 2026-06-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 547

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bemarituzumab with mFOLFOX6	Bemarituzumab	-
Bemarituzumab with mFOLFOX6	mFOLFOX6	-
Placebo with mFOLFOX6	mFOLFOX6	-
Placebo with mFOLFOX6	Placebo	-

Primary Outcome Measures

Name	Time	Method
Overall Survival	Up to approximately 3.5 years	Overall survival in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Secondary Outcome Measures

Name	Time	Method
Number of Participants with an Anti-bemarituzumab Antibody Formation	Day 1 up to approximately 3.5 years
Progression-free Survival (PFS)	Up to approximately 3.5 years	PFS in all randomized participants
Objective Response Rate (ORR)	Up to approximately 3.5 years	ORR in all randomized participants
Mean Subjective Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)	Baseline up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
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)	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Mean Subjective Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
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
Disease Control Rate	Up to approximately 3.5 years	Disease Control Rate in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)	Up to approximately 3.5 years	Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests after first dose will be recorded as TEAEs.
Overall Survival	Up to approximately 3.5 years	Overall survival in all randomized participants
Duration of Response (DOR)	Up to approximately 3.5 years	DOR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
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)	Baseline up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
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)	Day 1 up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Change from Baseline of Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)	Baseline up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
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)	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score	Up to approximately 3.5 years	Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Trial Locations

Locations (299)

Alaska Oncology and Hematology; 🇺🇸 Anchorage, Alaska, United States

Mayo Clinic Arizona; 🇺🇸 Phoenix, Arizona, United States

The Oncology Institute Clinical Research; 🇺🇸 Cerritos, California, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Saint Francis Medical Group; 🇺🇸 Indianapolis, Indiana, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Healthier Hematology and Oncology Excelsior Integrated Medical Group; 🇺🇸 Brooklyn, New York, United States

White Plains Hospital Center for Cancer Care; 🇺🇸 White Plains, New York, United States

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