. 2025 Jun;21(13):1613-1623.

doi: 10.1080/14796694.2025.2496133. Epub 2025 May 5.

DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients

François Cherifi¹, Isabelle Ray-Coquard², Maria Jesus Rubio³, Xavier Paoletti⁴, Domenica Lorusso^{5

6}, Chel Hun Choi⁷, Kosei Hasegawa⁸, David Shao Peng Tan⁹, Emma Hudson¹⁰, Alison Davis¹¹, Germana Tognon¹², Stéphanie Lheureux¹³, Mehmet Ali Vardar Key¹⁴, Jean Emmanuel Kurtz¹⁵, Jerome Alexandre¹⁶, Florence Joly¹⁷

Affiliations

¹ Clinical Research Department, Centre François Baclesse, Caen, France.
² Léon Bérard Center, University of Claude Bernard Lyon Est, Lyon, France.
³ Servicio de Oncología Médica, Hospital Universitario Reina Sofía, Córdoba, Spain.
⁴ Biostatistic Unit, Institut Curie, Paris, France.
⁵ Gynecologic Oncology Unit, Humanitas San Pio X, Milan, Italy.
⁶ Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy.
⁷ Samsung Medical Center, Sungkyunkwan Univ, Gangnam-Gu, Republic of (South) Korea.
⁸ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
⁹ National University Cancer Institute, National University Hospital and National University of Singapore (NUS) Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
¹⁰ Gynaecologic Oncology, Velindre Cancer Centre, Cardiff, WLS, UK.
¹¹ Department of Medical Oncology, Canberra Hospital, Canberra, Australia.
¹² UO Ostetricia-Ginecologia ASST Spedali Civili, Università degli Studi-Brescia, Brescia, Italy.
¹³ Princess Margaret Hospital, Department of Medical Oncology, Toronto, ON, Canada.
¹⁴ Department of Gynecologic Oncology, Balcalı Hospital, Adana, Turkey.
¹⁵ Haematology-Oncology Department, Centre Hospitalier Régional et Universitaire de Strasbourg Hôpital Civil, Strasbourg, France.
¹⁶ Medical Oncology Department, AP-HP-centre Université de Paris Cité, Paris, France.
¹⁷ Medical Oncology Department, CHU de Caen, Caen, France.

PMID: 40323277
PMCID: PMC12140448 (available on 2026-05-05)
DOI: 10.1080/14796694.2025.2496133

DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients

François Cherifi et al. Future Oncol. 2025 Jun.

. 2025 Jun;21(13):1613-1623.

doi: 10.1080/14796694.2025.2496133. Epub 2025 May 5.

Authors

Affiliations

¹ Clinical Research Department, Centre François Baclesse, Caen, France.
² Léon Bérard Center, University of Claude Bernard Lyon Est, Lyon, France.
³ Servicio de Oncología Médica, Hospital Universitario Reina Sofía, Córdoba, Spain.
⁴ Biostatistic Unit, Institut Curie, Paris, France.
⁵ Gynecologic Oncology Unit, Humanitas San Pio X, Milan, Italy.
⁶ Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy.
⁷ Samsung Medical Center, Sungkyunkwan Univ, Gangnam-Gu, Republic of (South) Korea.
⁸ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
⁹ National University Cancer Institute, National University Hospital and National University of Singapore (NUS) Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
¹⁰ Gynaecologic Oncology, Velindre Cancer Centre, Cardiff, WLS, UK.
¹¹ Department of Medical Oncology, Canberra Hospital, Canberra, Australia.
¹² UO Ostetricia-Ginecologia ASST Spedali Civili, Università degli Studi-Brescia, Brescia, Italy.
¹³ Princess Margaret Hospital, Department of Medical Oncology, Toronto, ON, Canada.
¹⁴ Department of Gynecologic Oncology, Balcalı Hospital, Adana, Turkey.
¹⁵ Haematology-Oncology Department, Centre Hospitalier Régional et Universitaire de Strasbourg Hôpital Civil, Strasbourg, France.
¹⁶ Medical Oncology Department, AP-HP-centre Université de Paris Cité, Paris, France.
¹⁷ Medical Oncology Department, CHU de Caen, Caen, France.

PMID: 40323277
PMCID: PMC12140448 (available on 2026-05-05)
DOI: 10.1080/14796694.2025.2496133

Abstract

Immunotherapy (IO) in endometrial cancer (EC) is the standard of care in the second line setting in combination with an anti-angiogenic agent. Randomized clinical trials have reported results supporting the addition of IO to chemotherapy (paclitaxel plus carboplatin) in the first-line setting in advanced EC patients in the global population, with high efficacy in mismatch repair deficient (MMRd) patients. These trials were not designed to answer this de-escalation question in the MMRd population, who benefit greatly from IO.The international, randomized phase III, DOMENICA trial compares first-line dostarlimab versus chemotherapy alone (with planned cross-over) for advanced MMRd EC. Our primary endpoint will be progression-free survival. The key secondary endpoints will be overall survival, safety and quality of life [NCT05201547].

Keywords: Mismatch repair deficient; advanced/metastatic; de-escalation; dostarlimab; endometrial cancer; immunotherapy; progression-free survival; treatment-related biomarkers.

Plain language summary

Endometrial cancer (EC) is divided into four biological sub-groups. One of them is defined by mismatch repair deficiency (MMRd). MMRd in cancer is associated with microsatellite instability and a high mutation rate, leading to the creation of numerous neo-antigens and a strong immune environment. Immunotherapy (IO) is associated with numerous successes for MMRd patients, such as in colorectal cancer. IO for EC is now the standard of care in the second-line setting in association with a tyrosine-kinase inhibitor after the result of the KEYNOTE-775 study. Four randomized studies have been conducted among advanced EC patients testing IO and chemotherapy in the first line (regardless of MMR status): RUBY with dostarlimab, NRG-GY-018 with pembrolizumab, AtTEnd with atezolizumab and DUO-E with durvalumab reporting positive result particularly in MMRd population. However, for MMRd patients, the benefit of adding chemotherapy to immunotherapy and the associated toxicity is not clear. Even more so when we take into account the characteristics of EC patients, often elderly with comorbidities (e.g.obesity, diabetes, etc)The ongoing phase 3 multicentric randomized DOMENICA trial will address the question of de-escalation by comparing carboplatin-paclitaxel to dostarlimab alone in the first-line setting in advanced MMRd EC. A cross-over to dostarlimab is planned in the chemotherapy group. Our primary endpoint will be progression-free survival. The key secondary endpoint will be overall survival. Other secondary endpoints will be safety and quality of life. Translational studies will be performed to explore immune biomarkers and the geriatric population.Registration number on ClinicalTrial.gov is [NCT05201547].

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Conflict of interest statement

Dr. Maria Jesus Rubio, Dr Chel Hun Choi, Dr. Alison Davis, Dr Xavier Paoletti, Dr. Mehmet Ali Vardar have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Dr. Germana Tognon’s honoraria/Consultation Fees: MSD, GSK

Dr Jean-Emmanuel Kurtz Honoraria/Consultation Fees: GSK, AstraZeneca, Eisai, MSD, AbbVie, Other Support: Close relative employed by MSD

Dr. David Shao Peng TanAdvisory Board Fees: AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, Daiichi Sankyo, Roche; Speaker Honoraria: AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, Takeda; Stock Ownership: Asian Microbiome Library (AMiLi); Institutional Research Grants: AstraZeneca, Bayer, Karyopharm Therapeutics, Roche; institutional Funding (PI): AstraZeneca, MSD, Eisai, Roche, Bergen Bio; Local PI Funding: Roche, BioNTech, PMV Pharma, GSK, Sutro Pharma, Bayer, Byondis B.V., Zeria Pharmaceutical; Non-Remunerated Roles: Chair, Asia Pacific Gynecologic Oncology Trials Group (APGOT), President, Gynecologic Cancer Group Singapore, Board of Directors, GCIG; Research Funding: NMRC Clinician Scientist Award, Pangestu Family Foundation; Non-Financial Interest: Product samples from AstraZeneca, Eisai, MSD

Dr. Emma Hudson Honoraria/Consultation Fees: AstraZeneca, MSD, GSK

Dr. Stéphanie Lheureux Grants/Contracts: AstraZeneca, Repare Therapeutics, GSK, Schrodinger, Merck, Roche, Seagen; Consulting Fees: Roche, Merck, GSK, Schrodinger, AstraZeneca, Seagen, Repare Therapeutics, Zai Lab, Gilead; Speaker Honoraria: GSK, AstraZeneca, Eisai

Dr. Domenica Lorusso Research Grants: Alkermes, AstraZeneca, Clovis, Coreept, Pharma&;, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, Pharmamar, Roche, Seagen; Honoraria/Consultation Fees: AstraZeneca, Clovis, Coreept, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, Sutro; Speaker’s Bureau: AstraZeneca, Clovis, Coreept, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, Sutro, Daiichi Sankyo, Novartis; Travel/Accommodation Expenses: AstraZeneca, Menarini, GSK, MSD

Pr Isabelle Ray-Coquard Research Grants: BMS, GSK, MSD; Honoraria/Consultation Fees: AstraZeneca, BMS, GSK, MSD, DSI Pharma&;, AbbVie, Corcept, Eisai, Zentalis, Novartis, Scorpion, Gilead, BioNTech

Dr. Kosei Hasegawa Consulting/Advisory Roles: Chugai, GSK, MSD, Regeneron, Roche, Sanofi; Speaker Honoraria: AstraZeneca, Chugai, MSD, Regeneron, Sanofi; Institutional Research Grants: MSD, Ono; Travel Expenses: Regeneron

Pr Alexandre Jerome Honoraria: Gilead, AstraZeneca,

Pr Florence Joly Research Grants: AstraZeneca (AZ); honoraria/Consultation Fees: AstraZeneca, GSK, Seagen, Roche, MSD, Eisai; Travel Expenses: GSK, Eisai, MSD

Dr. François Cherifi Honoraria: Gilead, AstraZeneca, MSD, Pharmamar; Institutional Research Grants: Novartis; Travel/Accommodation Expenses: Gilead, Pharmamar, AstraZeneca, MSD, Roche Chugai

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DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients

Affiliations

DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients

Authors

Affiliations

Abstract

Plain language summary

Conflict of interest statement

References

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