Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (FORTITUDE-101)

Amgen

Status and phase: Active, not recruiting; Phase 3

Conditions: Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Treatments: Drug: Bemarituzumab; Drug: mFOLFOX6; Drug: Placebo

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT05052801

2023-505457-40 (Registry Identifier)

20210096

Details and patient eligibility

About

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)

Enrollment: 516 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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516 participants in 2 patient groups

Bemarituzumab with mFOLFOX6

Experimental group

Treatment:

Drug: mFOLFOX6

Drug: Bemarituzumab

Placebo with mFOLFOX6

Active Comparator group

Treatment:

Drug: Placebo

Drug: mFOLFOX6