Trial details

Trial short name: FORTITUDE 101

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 (FORTITUDE-101)

Principal Investigator: Dr. Michael Raphael

Cancer type: Gastrointestinal
Cancer location: Gastrointestinal
Disease stage: Early Cancer
Trial phase: Phase 3
Intervention: Bemarituzumab (AMG 552)

Registration #: NCT05052801

Trial description:
Fibroblast growth factor receptor 2b (FGFR2b) is a splice variant of the FGFR receptor and is overexpressed in approximately 30% of non-human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC) (Wainberg et al, 2021). Bemarituzumab is a humanized monoclonal antibody specific to the human FGFR2b receptor that blocks fibroblast growth factor (FGF) ligand binding to the receptor. In a randomized doubleblind phase 2 trial, Study FPA144-004, bemarituzumab combined with oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX6) chemotherapy demonstrated longer progression-free survival (PFS) and overall survival (OS) as well as a greater objective response rate (ORR) compared to mFOLFOX6 plus placebo. Consistent with the hypothesis that bemarituzumab benefit is derived through its interaction with the FGFR2b receptor is the observed greater improvement associated with higher levels of FGFR2b. Evaluation of bemarituzumab in subjects with GC whose tumors have FGFR2b overexpression may improve the outcome for these subjects.

Inclusion Criteria: •Adults with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy •Fibroblast growth factor receptor 2b (FGFR2b) overexpression positive 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 •Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer