Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer. (FORTITUDE-102)

Amgen

Status and phase: Active, not recruiting; Phase 3

Conditions: Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Treatments: Other: Placebo; Drug: Nivolumab; Drug: Chemotherapy; Drug: Bemarituzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05111626

20210098

2023-505458-16 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 507 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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

Additional Inclusion Criteria Part 2:

• No prior treatment for metastatic or unresectable disease except for a maximum of

  1 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.

Exclusion Criteria:

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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507 participants in 3 patient groups, including a placebo group

Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab

Experimental group

Description:

Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK).

Treatment:

Drug: Bemarituzumab

Drug: Chemotherapy

Drug: Nivolumab

Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab

Experimental group

Description:

Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle.

Treatment:

Drug: Bemarituzumab

Drug: Chemotherapy

Drug: Nivolumab

Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab

Placebo Comparator group

Description:

Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle.

Treatment:

Drug: Chemotherapy

Other: Placebo

Drug: Nivolumab