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-DE
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-02-10
• Last Update Posted: 26 February 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 prescreening informed consent) or a fresh biopsy.
- For subjects receiving CAPOX only, the ability to take oral medication.
- 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 autoimmun

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

Please refer to protocol for remaining exclusion criteria

Study & Design

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