Resumen

The main objective of Part 1 is to evaluate the safety and tolerability of bemarituzumab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) and nivolumab. The main objective Part 2 is to compare efficacy of bemarituzumab plus chemotherapy (mFOLFOX6 or capecitabine combined with oxaliplatin (CAPOX)) and nivolumab to placebo plus chemotherapy (mFOLFOX6 or CAPOX) and nivolumab as assessed by overall survival.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 100 YearsSexo: ALL

Criterios de inclusión

Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
Participant has no contraindications to nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Participants in Part 1 must have no contraindications to mFOLFOX6. Participants in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Participants in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist
Adequate organ function as follows:
Absolute neutrophil count ≥ 1.5 x 10\^9/L
Platelet count ≥ 100 x 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 aminotransaminase (AST) and Alanine aminotransaminase (ALT) \<3 x upper limit of normal (ULN) (or \< 5 x ULN if liver involvement)
Total bilirubin \<1.5 x ULN (or \< 2 x ULN if liver involvement or Gilbert's disease)
Part 1 only: Calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/minute calculated using the formula of Cockcroft and Gault (\[140 - Age\] × Mass \[kg\]/\[72 × Creatinine mg/dL\]) (x 0.85 if female).
Part 2 only: 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).
INR or prothrombin time (PT) \< 1.5 × ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment
No prior treatment for metastatic or unresectable disease except for a maximum of
dose of chemotherapy with or without nivolumab; prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment
Fibroblast growth factor receptor 2b (FGFR2b) ≥ 10% 2+/3+ tumor cells (TC) 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.

Criterios de exclusión

Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
Known positive human epidermal growth factor receptor 2 (HER2) status
Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
Peripheral sensory neuropathy grade 2 or higher
Clinically significant cardiac disease
Other malignancy within the last 2 years (exceptions for definitively treated disease)
Chronic or systemic ophthalmologic disorders
Major surgery or other investigational study within 28 days prior to randomization
Palliative radiotherapy within 14 days prior to randomization
Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study

Intervenciones

drug

Bemarituzumab

Bemarituzumab will be administered as intravenous (IV) infusion.

drug

Nivolumab

Nivolumab will be administered as IV infusion.

drug

Chemotherapy

mFOLFOX6: 5-fluorouracil, leucovorin, and oxaliplatin will be administered as IV infusion. OR CAPOX: oxaliplatin will be administered as IV infusion and capecitabine will be administered orally.

other

Placebo

Placebo will be administered as IV infusion.

Ubicaciones

Cemic

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

Centro Medico Austral

Buenos Aires, Distrito Federal, Argentina

Fundacion Ars Medica

San Salvador de Jujuy, Jujuy Province, Argentina

Clinica Viedma

Viedma, Río Negro Province, Argentina

Hospital Provincial del Centenario

Rosario, Santa Fe Province, Argentina

Exelsus Oncologia Clinica

San Miguel de Tucumán, Tucumán Province, Argentina

Fundacion Respirar

Buenos Aires, Argentina

Hospital Italiano

Capital Federal, Argentina

Sanatorio Allende

Córdoba, Argentina

Hospital Privado Universitario de Cordoba

Córdoba, Argentina

Centro Oncologico Riojano Integral

La Rioja, Argentina

A Phase 1b/3 Study of Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab Alone in Subjects With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer With FGFR2b Overexpression

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Bemarituzumab

Nivolumab

Chemotherapy

Placebo

Ubicaciones

Cemic

Hospital Italiano de La Plata

Centro Medico Austral

Fundacion Ars Medica

Clinica Viedma

Hospital Provincial del Centenario

Exelsus Oncologia Clinica

Fundacion Respirar

Hospital Italiano

Sanatorio Allende

Hospital Privado Universitario de Cordoba

Centro Oncologico Riojano Integral

Patrocinadores