Peri-operative Treatment of Resectable Gastroesophageal Cancer Using Bemarituzumab (BEMA) Plus Perioperative Treatment

Phase 1

Not yet recruiting

• Conditions: GastroEsophageal Cancer
• Interventions: Drug: Bemarituzumab

• Registration Number: NCT06978062
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

This is an open-label,multi-centre, phase 1b safety and feasibility study aiming to assess the safey and feasibility of bemarituzumab plus chemiotherapy (FLOT) for the peri-operative treatment of resectable gastroesophageal cancer. Participants will firstly be centrally screened for FGFR2b expression After FGFR2b testing, participants bearing FGFR2b overexpression, and meeting the remainder of the eligibility criteria will be enrolled in the trial.Participants will receive 4 administrations of FLOT chemotherapy in combination with bemarituzumab. Following this neo-adjuvant part, patients should undergo surgery. Following surgery, patients will receive 4 administrations of FLOT chemotherapy in combination with bemarituzumab. Imaging will be performed every 3 months for the first 2 years and thereafter every 6 months as per standard of care.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-04-29
• Status Verified: 2025-05
• Study First Submitted QC: 2025-05-09
• Last Update Submitted: 2025-05-09
• Study First Posted: 2025-05-18
• Last Update Posted: 2025-05-18
• Study Start: 2026-02-20
• Primary Completion: 2028-09-11
• Study Completion: 2029-09-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

• Signed screening informed consent
• Age ≥ 18 years
• Availability of a diagnostic tumour sample for central evaluation (FFPE block or minimum 10 slides).
• Histologically proven, previously untreated, locally advanced, resectable gastric/GEJ adenocarcinoma cT2-cT4, N0, M0 or cTany, N+, M0. Note: if the results of the staging laparoscopy are pending at this stage it is acceptable to include the patients in this step, in the interest of patient time-to-treatment.
• Planned peri-operative treatment with FLOT chemotherapy and surgically assessed feasible R0 resection
• Centrally confirmed FGFR2b overexpression as defined by ≥10% tumour cells with 2+/3+ FGFR2b staining by immunohistochemistry (IHC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Previously untreated, locally advanced, histologically confirmed, resectable gastric/GEJ adenocarcinoma cT2-cT4, N0, M0 or cTany, N+, M0 by radiological and surgical staging
• Adequate hematologic and organ function

Exclusion Criteria

• Prior anticancer treatment for the disease under investigation
• History or evidence of systemic disease or ophthalmological disorders requiring chronic use of ophthalmologic corticosteroids
• Evidence of any ongoing ophthalmologic abnormalities or symptoms that are recent (within 4weeks) or actively progressing
• Unwillingness to avoid the use of contact lenses during study treatment and follow-up period of at least 100 days after end of treatment.
• 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 ophthalmologic laser treatment
• History of solid organ transplantation
• History of interstitial lung disease
• 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
• Patients on immunosuppressive therapy or having immune system disorders, including auto-immune diseases. Concurrent steroid use of not more than an equivalent of 10 mg/day prednisolone is allowed. Inhaled, intranasal, intraocular, and/or joint injections of corticosteroids are allowed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FLOT plus Bemarituzumab	Bemarituzumab	* FLOT will be administered every 2 weeks (Q2W). Docetaxel 50 mg/m2 is given as 1 hour infusion, followed by Oxaliplatin 85mg/m2 as a 2-hour infusion, leucovorin 200 mg/m2 over 2 hours and 5-FU 2600 mg/m2 as a 24 hour-infusion, * Bemarituzumab will be given as a 30min infusion 15 mg/kg every 2 weeks (Q2W) with an additional 7.5 mg/kg dose on cycle 1 day 8.

Primary Outcome Measures

Name	Time	Method
Completion rate of neoadjuvant treatment followed by surgery without serious anastomotic leakage, defined as the percentage of patients who completed the treatment without grade 2 or more anastomotic leakage as per Clavien-Dindo Classification	2.3 years from first patient in	Patients will be considered to have successfully completed the neo-adjuvant treatment if they complete the 4 cycles of FLOT plus Bemarituzumab. Additionally, anastomotic leakage will be reported as post-surgery complication following the modified Clavien-Dindo Classification

Secondary Outcome Measures

Name	Time	Method
Major pathological response	3.6 years from first patients in	Major pathological response rate will be computed as the percentage of patients who had major tumour regression (\< 10% vital residual tumour cells) after neoadjuvant treatment.
Treatment-emergent adverse events	3.6 years from first patients in
Pathological complete response	3.6 years from first patients in
Overall survival (OS)	3.6 years from first patients in	Overall survival will be computed from the date of enrolment to the date of death
R0 resection	3.6 years from first patients in
Progression free survival (PFS)	3.6 years from first patients in	Progression-free survival is defined as the time interval from enrolment to the first event of progression/recurrence
Completion rate of neoadjuvant and adjuvant therapy	3.6 years from first patients in
Postoperative complications according to CLAVIEN DINDO classification	3.6 years from first patients in
30 and 90 day-mortality after surgery	1.7 years from first patients in