bemarituzumab or placebo plus chemotherapy in gastric cancers with fibroblast growth factor receptor 2b (fgfr2b) overexpression

Conditions: Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

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)


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.

Keywords: gastric cancer gastroesophageal junction adenocarcinoma bemarituzumab fgfr2b overexpression