Bemarituzumab plus Chemotherapy and Nivolumab versus Chemotherapy and Nivolumab Alone

Phase 1

• Conditions: ntreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression; MedDRA version: 21.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.1Level: LLTClassification code 10084227Term: Gastroesophageal junction cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-003477-61-BG
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-10
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 528

Inclusion 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)
- 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.
Part 2 only: Calculated or measured creatinine clearance (CrCl) of = 30 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.
Subject has no contraindications to nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Subjects in Part 1 must have no contraindications to mFOLFOX6. Subjects in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Subjects in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist.

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.
- Confirmed FGFR2b = 10% 2+/3+ TC 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.
- For subjects receiving CAPOX only, the ability to take oral medication.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 406
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 122

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
- -Evidence of, or recent (within 6 months) history 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. Recent (within 6 months) corneal surgery or ophthalmic laser treatment.
- 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.
- For subjects receiving CAPOX only, GI tract disease causing the
inability to take oral medication, malabsorption syndrome, or
requirement for IV alimentation, or uncontrolled inflammatory GI
disease (eg, Crohn's disease, ulcerative colitis).
Please refer to protocol for remaining exclusion criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified