Open-label non-randomized multicentric phase 2 study evaluating the combination of bemarituzumab + FLOT chemotherapy in perioperative setting for resectable stage cT2-T4a or N+ gastric and GEJ adenocarcinoma overexpressing FGFR2b (BEMAFLOT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Cancerologie De L Ouest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

completed 7 Nov 2025

Decision date (initial)

2025-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCa · AMGEN

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

to evaluate the efficacy of a combination of FLOT chemotherapy with bemarituzumab as perioperative treatment for gastric and GEJ adenocarcinoma

Secondary objectives 8

1. To assess the safety and tolerability of the combination of FLOT + bemarituzumab
2. To measure the rate of severe post-operative complications
3. To describe histological impact of the combination of FLOT + bemarituzumab
4. To describe survival impact (Overall Survival – OS and Disease-Free Survival – DFS) of the combination of FLOT + bemarituzumab
5. To describe time to recurrence (TTR) and to describe pattern of recurrence
6. To measure the Global Health Status and Physical functioning
7. To describe the nutritional status
8. To explore association between expression of FGFR2b and OS and DFS

Conditions and MedDRA coding

gastric and gastro-oesophageal junction adenocarcinomas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1) Participants must have signed and dated an informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. A signed informed consent must be obtained prior to conducting any study-specific procedures
2. 2) Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
3. 3) Participants must have histologically confirmed diagnosis of gastric or gastroesophageal junction (Siewert 2-3) adenocarcinoma
4. 4) Tumour archival tissue must be provided for analysis of FGFR2b overexpression prior to inclusion
5. 5) Positive FGFR2b overexpression status by immunohistochemistry was defined as exhibiting any moderate (2+) to strong (3+) membranous staining in ≥ 10% of tumour cells.
6. 6) ECOG performance status score of 0 or 1
7. 7) cT2-T4a or N+ made by CT scan and endoscopic ultrasound and according to UICC 8e edition gastric or gastroesophageal junction (Siewert 2-3) adenocarcinoma without distant metastases (M0), without infiltration of adjacent structures or organs. If peritoneal carcinomatosis is clinically suspected, laparoscopic exclusion of peritoneal carcinomatosis is mandatory
8. 8) Adequate hematologic and organ function as assessed by the following laboratory tests perfor if Gilbert’s syndrome is documented  Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN  Albumin ≥ 30 g/L Bone Marrow Function  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L  Platelet count ≥ 100 x 10^9/L  Haemoglobin ≥ 9 g/dL (med within 7 days before start of study treatment: Hepatic Function  Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowedwithout transfusion support within 7 days before the first dose of study treatment) Red blood cell (pRBC) transfusion is allowed if Hb meets the criteria for at least 7 days after transfusion. Renal Function  Serum creatinine ≤1.5 x ULN AND creatinine clearance ≥50 mL/min (measured or calculated using the CDK-EPI formula) Coagulation  International normalized ratio (INR) or prothrombin time < 1.5 × ULN except for subjects receiving anticoagulation therapy, who must be on stable dose of anticoagulant therapy for 6 weeks before enrolment
9. 9) Male and female adult participants 18 years of age or more
10. 10) Affiliated to French social regimen
11. 11) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception during treatment and for an additional 90 days after the last dose of bemarituzumab, 15 months after the end of the treatment with oxaliplatin, 6 months after the end of the treatment with fluorouracil, 2 months after the end of the treatment with docetaxel
12. 12) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study intervention during treatment and for an additional 6 months after the last dose of bemarituzumab, 12 months after the end of the treatment with oxaliplatin, 3 months after the end of the treatment with fluorouracil and 4 months after the end of the treatment with docetaxel 1. Distant metastases or infiltration of adjacent structures or

Exclusion criteria 31

1. 1) Distant metastases or infiltration of adjacent structures or organs and all primarily non-resectable stages. Patients with enlarged, metastasis suspected, para-aortal, mesenterial or para pancreatic lymph nodes are M1 and must not be enrolled into the trial
2. 10) Prior immunosuppressive therapy: immunosuppressive doses of systemic medications of > 10 mg/day of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dose corticosteroids and/or continuous low dose of prednisone (< 10 mg/day) are permitted. In addition, inhaled, intranasal, and/or joint injections of corticosteroids are allowed.
3. 11) Chronic inflammatory intestinal disease
4. 12) Known allergy, hypersensitivity or contraindication against 5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel or Bemarituzumab
5. 13) Severe acute disease or active infection requiring systemic treatment or any uncontrolled infection within 14 days before the first dose of study treatment
6. 14) History of cardiac disorders as defined by: - Congestive heart failure ≥ New York Heart Association (NYHA) class 2 ; - Acute myocardial infarction < 6 months prior or evolutive cardiopathy to the first dose of study treatment ; - Unstable angina within 6 months before the first dose of study treatment, acute myocardial infarction < 6 months prior to the first dose of study treatment ; - Uncontrolled hypertension (defined as an average systolic blood pressure >160 mmHg or diastolic >100 mm Hg despite optimal treatment (measured following European Society for Hypertension/European Society of Cardiology [ESH/ESC] 2018 guidelines); - Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease, QTc ≥ 470ms
7. 16) Any haemorrhage or bleeding event ≥ NCI-CTCAE Grade 3 within 28 days prior to the start of study treatment
8. 17) Known human immunodeficiency virus infection with CD4+ T cell counts < 350 cells/µL, hepatitis C infection (subjects with hepatitis C who achieve a sustained virologic response following antiviral therapy are permitted), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody who achieve sustained virologic response with antiviral therapy directed at hepatitis B are permitted)
9. 18) Subjects who experienced severe, life-threatening, or recurrent (Grade 2 or higher) immune-mediated adverse events (AEs) or infusion-related reactions including those that led to permanent discontinuation while on treatment with immune-oncology agents
10. 19) History of other malignancy within the past 2 years with exception of skin non melanoma cancer and in situ carcinoma of cervix
11. 20) Major contra indication to surgery including cirrhosis, oesophageal varices, severe respiratory insufficiency VEMS <1L and severe obliterating arteriopathy of the lower limbs.
12. 2) Loss of body weight ≥10% in the month before inclusion
13. 21) Partial or total DPD deficiency
14. 22) History or evidence of any other clinically significant disorders, conditions, or diseases that in the opinion of the investigator or sponsor, if consulted, would pose a risk to subject safety, or interfere with study procedures or completion
15. 23) Participation in another therapeutic clinical study or receiving any investigational agent within 28 days of enrolment or during this clinical study
16. 26) Female subjects of childbearing potential unwilling to use highly effective methods of contraception during treatment and for an additional 90 days after the last dose of bemarituzumab15 months after the end of the treatment with oxaliplatin, - 6 months after the end of the treatment with fluorouracil - 2 months after the end of the treatment with docetaxel
17. 27) Female subjects who are breastfeeding or who plan to breastfeed while on the study through 90 days after the last dose of bemarituzumab
18. 28) Female subjects planning to conceive while on the study through 90 days after the last dose of bemarituzumab
19. 30) Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test
20. 31) Subject likely to be unavailable to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge
21. 3) Other histology than adenocarcinoma
22. 4) Tumour with microsatellite instable disease detected by ICH or NGS are excluded
23. 5) History of peripheral neuropathy with symptoms≥ grade 2
24. 6) Known allergy, hypersensitivity or contraindication to components of bemarituzumab formulation including polysorbate
25. 7) History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
26. 8) Ocular related disorders:  History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids  Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or are actively progressing  Recent (within 6 months) corneal surgery or ophthalmic laser treatment or recent (within 6 months) history of, or evidence of, corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
27. 9) Unwillingness to avoid use of contact lenses during study treatment and for ≥ 100 days after the end of treatment
28. 15) No reversible electrolyte disorders such as hypokalemia, hypocalcemia or hypomagnesemia
29. 24) Live attenuated vaccines
30. 25) Recent (in the last 4 weeks) or concomitant treatment with brivudine
31. 29)Male who are sexually active with WOCBP unwilling to use highly effective methods of contraception during treatment and for an additional 90 days after the last dose of bemarituzumab during treatment, 12 months after the end of the treatment with oxaliplatin,3 months after the end of the treatment with fluorouracil, 4 months after the end of the treatment with docetaxel

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the complete pathological response in histological result of primary tumour and lymph nodes from the surgical resection, using Becker tumour resection grading (21).

Secondary endpoints 8

1. Adverse Events (AE), Serious Adverse Events (SAE), assessed by CTCAE version 5.0 and specific grading for ocular toxicity cf. section .9.1.1 (start, imputability)
2. Post-operative complications, graded using Clavien-Dindo scale, between surgery and 30 days postoperative
3. Histological results of the primary tumour and lymph nodes from the surgical resection, using Becker tumour grading
4. • Vital status throughout the 5 years follow-up • TDM every 3 months for 2 years and every 6 months until 5 years of follow-up. Recurrence is defined according to RECIST 1.1.
5. • Vital status throughout the 5 years follow-up • TDM every 3 months for 2 years and every 6 months until the 5-years-follow-up. Recurrence is defined according RECIST 1.1.
6. EORTC QLQ-C30 at C1D1, after surgery, at the end of treatment (EOT) visit and then every 6 months for 5 years.
7. The nutritional status assessment will be assessed by Mini Nutritional Assessment (MNA)(23), at C1D1, after surgery, at the EOT visit and every 6 months for 5 years. The MNA (23–26) provided a global score of nutritional status from 0 to 30 and identify 3 categories: normal (≥24), at risk of malnutrition (≥17) and malnourished (<17).
8. • The expression of FGFR2b is measured prior to inclusion in the trial, during the screening period. • Vital status throughout the 5 years follow-up • TDM every 3 months for 2 years and every 6 months until the 5-years-follow-up. Recurrence is defined according RECIST 1.1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Cancerologie De L Ouest

Sponsor organisation

Institut De Cancerologie De L Ouest

Address

Boulevard Jacques Monod

City

Saint-Herblain Cedex

Postcode

44805

Country

France

Scientific contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Judith RAIMBOURG

Public contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Marine TIGREAT

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications