20210098 - FORTITUDE-102 - 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

Studio Clinico

Patologia: Neoplasie dello stomaco, Tumori dell’esofago

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Prima linea

Criteri di inclusione: 

Inclusion Criteria Part 1 and Part 2:

- 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 mFOLFOX6 chemotherapy or nivolumab
- 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)
    - Calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/minute calculated using the formula of Cockcroft and Gault
    - International Normalized Ratio (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

Additional Inclusion Criteria Part 2:

- No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 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.

Criteri di esclusione: 

- 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.

Trattamento sperimentale: 

- Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab
 Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the   recommended phase 3 dose (RP3D) based on occurence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK).
- Part 2: Bemarituzumab with mFOLFOX6 and Nivolumab
Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab.

Trattamento di controllo: 

- Part 2: Placebo with mFOLFOX6 and Nivolumab
Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab.

Obiettivi primari dello studio: 

- 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 mFOLFOX6 and nivolumab to placebo plus mFOLFOX6 and nivolumab as assessed by overall survival.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT05111626

Data di inserimento: 23.02.2023

Data di aggiornamento: 24.01.2024

Promotore

Amgen

Principal Investigator ITALIA

ASST Papa Giovanni XXIII, Bergamo

Riferimento: Dr.ssa Stefania Mosconi

Telefono: 0352673688

Email: smosconi@asst-pg23.it

Localita: Bergamo