PRODIGE 111 – DOMZIGAST A randomized phase II study evaluating FOLFIRI vs FOLFIRI plus Domvanalimab (anti-TIGIT) and Zimberelimab (anti-PD1) in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma with progression during or after peri-operative chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

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 12 Dec 2025

Decision date (initial)

2025-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GILEAD

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The main objective is to evaluate the progression-free survival (PFS) with FOLFIRI plus Zimberelimab and Domvanalimab versus FOLFIRI in patients with advanced-stage gastric or gastro-oesophageal junction or oesophageal adenocarcinoma who progressed/recurred (based on RECIST 1.1 evaluated by the investigator) during or with 6 months of platinum-based peri-operative treatment.

Secondary objectives 6

1. Progression-free survival (PFS) (median)
2. Overall survival (OS)
3. Safety profile
4. Quality of life (QoL): QLQ-C30 version 3.0 and QLQ-STO22 questionnaires
5. Time to progression (TTP)
6. Best objective response rate (BOR)

Conditions and MedDRA coding

stomach cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Age ≥ 18 years
2. At least one measurable lesion as assessed by CT-scan or MRI according to RECIST 1.1 criteria
3. World Health Organization (WHO) performance status 0-1
4. Adequate organ and marrow function, as defined by the following laboratory values: Neutrophils ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x upper limit of normal (ULN) if there is no hepatic metastasis; ≤ 5x ULN with hepatic metastases, Alkaline phosphatase ≤ 5x ULN, Total bilirubin ≤ 1.5 ULN, Creatinine clearance ≥ 50 mL/min according to the CDK-EPI formula, Albumin > 28g/L
5. Individuals of childbearing potential must agree to use two medically acceptable contraception methods—one for themselves and one for their partner—during the study and for six months following the last treatment dose intake
6. Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures
7. Patient who is a beneficiary of the social security system
8. Histologically proven locally advanced unresectable or metastatic gastric, esophagogastric junction (GEJ) or esophageal adenocarcinoma
9. HER2 negative tumor
10. pMMR (immunohistochemistry of the 4 MMR protein) and/or MSS (PCR or NGS test) status
11. Known PD-L1 CPS (patients are eligible whatever the CPS score and CPS must be performed on the most recent tumor sample)
12. Available tumor sample (before or after peri-operative treatment, archival or new tumor sample)
13. Participation to all ancillary studies is mandatory
14. Progression during or within 6 months after pre-operative, peri-operative or post-operative platinum-based therapy (i.e., FLOT, 5FU cisplatin or FOLFOX regimen) alone or combined with radiation
15. Eligible for a treatment with irinotecan and 5-FU
16. Patients must not be eligible for an approuved treatment with a combination of conjugated antibody drugs plus chemotherapy or immunotherapy plus chemotherapy

Exclusion criteria 30

1. Concurrent enrolment in another clinical study – unless it is an observational study or during the follow-up period of an interventional study
2. Treatment with sorivudine and others analogues as brivudine (irreversibly inhibits the enzyme dihydropyrimidine dehydrogenase) within 4 weeks prior the first dose of treatment
3. Strong inducers of CYP3A4 and/or UGT1A1 and strong inhibitor of CYP3A4 within 7 days prior the first dose of treatment or known Gilbert disease: Strong inducers of CYP3A4 (treatment with St John’s Wort (Hypericum perforatum), fampicin, phenobarbital, primidone, phenytoin and carbamazepine (Appendix 12). Strong inhibitors of CYP3A4, continuous use of azole antifungals (posaconazole, voriconazole, itraconazole, isavuconazole), ritonavir, verapamil, diltiazem, grapefruit juice (equivalent to half a fresh grapefruit/day) (Appendix 12).
4. History of chronic inflammatory bowel disease (IBD) or intestinal obstruction
5. Any unresolved significant toxicity NCI CTCAE v5.0 ≥ grade 2 from previous anticancer therapy (excepted neuropathy and alopecia)
6. History of trauma or major surgery within 28 days prior to randomization (placement of central venous access catheter is not considered a major surgical procedure)
7. Active or prior documented serious autoimmune or inflammatory disorders that required systemic treatment in the past 2 years (e.g., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy or inflammatory disorders. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment as listed above
8. Active viral, bacterial or fungal infections requiring parenteral treatment within 14 days of randomization. Prophylactic antibiotic treatment (e.g., to prevent a urinary tract infection) is allowed
9. Vaccinations with live vaccine within 28 days prior to the start of treatment
10. History of idiopathic pulmonary fibrosis, interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis, drug-induced pneumonitis, organizing pneumonia or evidence of active pneumonitis on screening chest CT-scan)
11. Active hepatitis B or C and active tuberculosis (in case of if positive viral load is detected)
12. Prior treatment by immune checkpoint inhibitor
13. Known immunodeficiency or HIV infection with HIV viral load ≥200 copies/mL or CD4+ T-cell count <350 cells/μL or taking medications that may interfere with metabolism of study drugs
14. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs (excepted: intranasal, inhaled, topical steroids or local steroid injection –at physiological dose that does not exceed 10 mg/day of prednisone or its equivalent – steroids as premedication for hypersensitivity reactions)
15. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer
16. Known untreated, symptomatic or actively progressing central nervous system (CNS) or leptomeningeal metastases (participants with treated brain metastases who are clinically stable and do not require steroid therapy for at least 14 days prior to the first dose of study intervention will not be excluded)
17. Clinically significant cardiovascular disease, cerebrovascular accident within 3 months prior to randomization, unstable angina or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization or unstable arrhythmia within 3 months prior to randomization
18. QTc interval > 480 msec
19. Poor nutritional status (weight loss of more than 10% during the last month)
20. Pregnant or breastfeeding woman, woman of childbearing potential not having had a negative pregnancy test ≤72hours prior to initiate the treatment,
21. Person deprived of liberty or under guardianship or incapable of giving consent
22. Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons
23. Prior treatment by irinotecan
24. Radiotherapy within 4 weeks prior to the first dose of treatment
25. Known hypersensitivity to any investigational product (IP), or any excipient contained in the formulations of the study drugs
26. HER2 2+
27. Treatment with phenytoin within 7 days prior the first dose of treatment
28. Dihydropyrimidine Dehydrogenase (DPD) deficiency defined by uracilemia level ≥ 16 ng/mL, if not previously done, blood uracil level must be performed at screening. Uracilemia dosing result is mandatory prior inclusion.
29. Known Uridine Diphosphate Glucuronyltransferase (UGT1A1) deficiency or known Gilbert disease
30. History of anterior organ transplant, including stem cell allograft

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the percentage of patients alive without progression at 6 months (PFS at 6 months) after the randomization. Progression is defined as radiological progression according to RECIST version 1.1 criteria from morphological assessment, according to the investigator, or death, whatever the reason (which occurs first).

Secondary endpoints 6

1. Overall survival (OS): OS is defined by the time between the date of randomization and the date of death (regardless of the cause). Alive patients will be censored at the date of their last news.
2. Time To Progression (TTP): This time is defined by the time between the date of randomization and the date of the first radiological progression (according to RECIST v1.1) according to the investigator or death linked to cancer (which occurs first). Patients alive without radiological progression will be censored on the date of their latest CT-scan. Patients who died for other reason than cancer will be censored at the date of death
3. Progression-Free Survival (PFS): PFS is defined as the time between randomization and first radiological progression (according to RECIST 1.1) or death (whatever the cause). Patients alive without progression will be censored at the date of last news. Median PFS is evaluated as secondary endpoint.
4. Best Objective Response Rate: It is the percentage of patients with Objective Response (OR) at the best response evaluation during the treatment according to RECIST v1.1 according to the investigator. The objective response is defined as partial or complete response. Patients without imaging or non-evaluable imaging will not be taken into account in the analysis.
5. Safety profile: Adverse events (AE) will be evaluated according to NCI-CTC v5.0. All grade and severe (grade 3-5) AE will be recorded until 4 months after the last administration of treatment.
6. Quality of life: Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30 and QLQ-STO-22 scales (at baseline, 3, 6, and 12 months). Scores will be described at inclusion by treatment arm. The time to final deterioration of the global health score will be calculated.Alive patients without deterioration of this score will be censored at the time of the last questionnaire received. Patients without questionnaire during follow-up will be censored at the date of randomization.

Investigational products

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

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon Cedex

Postcode

21001

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Locations

1 EU/EEA country · 29 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

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