Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line

NCT05201547 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: GINECO-EN105b
• Study Type: interventional
• Target: 260
• Locations: 10 countries
• Sites: 100

Brief Summary

Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient relapse or advanced endometrial cancer.

Conditions

Endometrial Cancer

Keywords

MMR; first line; metastatic; dostarlimab

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Defined as the time from the date of randomization until objective tumor progression based on RECIST 1.1, by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first. Patients alive and free of progression will be censored at the last disease assessment date.

  from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years.

Secondary Outcomes (14)

• Overall Survival (OS) (key secondary endpoint)

  from the date of randomization until death due to any cause, assessed up to 5 years

• Progression Free Survival 2 (PFS2)

  from the date of randomization until second objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years

• Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version)

  through study completion, an average of 5 years

• To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30)

  Defined as the Global Health Status score from the EORTC QLQ C30 at 18 weeks, assessed up to 5 years

• To assess the quantity of peripheral neuropathy event induced by chemotherapy based on EORTC QLQ-CIPN 20 (Quality of Life questionnaire-Chemotherapy induced peripheral neuropathy 20)

  Defined as the Global Health Status score from the EORTC QLQ-CIP20 at 18 weeks, assessed up to 5 years

Study Arms (2)

Arm A: Dostarlimab 500 mg, every 3 weeks, 4 cycles and then 1000 mg every 6 weeks

EXPERIMENTAL

Drug: Dostarlimab

Arm B: Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2, every 3 weeks, 6 cycles.

EXPERIMENTAL

Drug: Carboplatin-Paclitaxel

Interventions

Carboplatin-Paclitaxel DRUG

Chemotherapy will be administered by intravenous infusion. Carboplatin AUC 5-6 + Pacltaxel 175 mg/m² every 3 weeks. Total duration of treatment: 6 cycles

Arm B: Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2, every 3 weeks, 6 cycles.

Dostarlimab DRUG

Dostarlimab will be administered through a 30-minute infusion at a dose of 500 mg Q3W from Cycle 1 through Cycle 4 and at a dose of 1,000 mg Q6W thereafter, beginning at Cycle 5 Day 1 up to a maximum of 2 years.

Arm A: Dostarlimab 500 mg, every 3 weeks, 4 cycles and then 1000 mg every 6 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must fulfil all the following criteria:
• Female patient is at least 18 years of age,
• Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
• Patient with histologically proven endometrial adenocarcinoma with recurrent or advanced disease.
• Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Patient must have primary Stage IIIA to C2 or Stage IV disease or first recurrent endometrial cancer (see International Federation of Gynecology and Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation therapy or surgery alone or in combination, and meet at least one of the following situations:
• Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative intent surgery or radiation.
• Patient has first recurrent disease and is chemotherapy naïve for this 1st recurrence or metastatic setting.
• Patient has recurrent disease and is chemotherapy naïve for recurrence or advanced /metastatic setting.
• Patient may have received prior irradiation for advanced endometrial cancer with or without radio-sensitizing chemotherapy if \> 3 weeks before the start of the study
• Patient with evaluable disease (measurable and not measurable disease) according to RECIST 1.1
• Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for the primary cancer and had a recurrence ≥ 6 months after completing treatment (first recurrence only).
• All histologic subtypes of endometrial adenocarcinoma could be included if MMRd/MSI-H
• Availability of 1 block for MMR/MSI status centralized confirmation for IHC or PCR/ NGS
• Patient could have been previously treated with hormone therapy, for the metastatic/advanced disease 12) Patient may have received pelvic and lombo-aortic external beam +/- vaginal brachytherapy

You may not qualify if:

• Patients are to be excluded from the study if they meet any of the following criteria:
• Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary Stage III or IV disease and has had a recurrence or PD within 6 months of completing this chemotherapy treatment prior to entering the study.
• Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do not exclude patients from study participation.
• Patient has had \> 1 recurrence of endometrial cancer, treated with chemotherapy. Surgery of the recurrence is allowed.
• Patient previously treated with systemic chemotherapy for non-curable advanced disease or metastatic disease
• Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Patient has received prior anticancer therapy for (advanced or metastatic disease (targeted therapies, hormonal therapy, radiotherapy) within 21 days or \< 5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter Note: Palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment may be allowed.
• Patient with contraindication to chemotherapy or checkpoint inhibitor treatments
• Patient has a concomitant malignancy, or patient has a prior non-endometrial invasive malignancy who has been disease-free for \< 3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
• Patient has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging \[using the identical imaging modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
• Patient has a known history of human immunodeficiency virus (HIV; HIV 1 or 2 antibodies).
• Patient has known active viral infection of hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid \[qualitative\] detection).
• Patient has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (eg, thyroid hormone or insulin).
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Patient has not recovered (ie, to Grade ≤ 1 or to baseline) from cytotoxic therapy-induced adverse events (AEs).

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• GlaxoSmithKline: collaborator

Study Sites (100)

Canberra Hospital

Garran, 2605, Australia

Location

Calvary Mater Newcastle

Waratah, 2298, Australia

Location

Princess Margaret Cancer Centre

Toronto, M5G2M9, Canada

Location

CHU d'Amiens - Hôpital Sud

Amiens, 80054, France

Location

Clinique de l'Europe

Amiens, 80090, France

Location

ICO Paul Papin

Angers, 49055, France

Location

Centre Hospitalier d'Auxerre

Auxerre, 89011, France

Location

Institut Sainte Catherine

Avignon, France

Location

CH Simone Veil de Beauvais

Beauvais, 60000, France

Location

CHRU Jean Minjoz

Besançon, 25000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

CHU Brest

Brest, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

ROC 37

Chambray-lès-Tours, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63000, France

Location

GHPSO

Creil, 60109, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 21079, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

CHU de Dijon

Dijon, 21079, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69310, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

APHM - Hôpital de la Timone

Marseille, 13005, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hôpital Saint-Joseph

Marseille, 13285, France

Location

Hôpital de Mont-de-Marsan

Mont-de-Marsan, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

Centre Azuréen de Cancérologie

Mougins, 06250, France

Location

Médipôle de NANCY SAS

Nancy, France

Location

Hôpital Privé du Confluent S.A.S.

Nantes, 44000, France

Location

Centre Antoine Lacassagne

Nice, 06100, France

Location

Institut de cancérologie du gard

Nîmes, 30029, France

Location

CHU d'ORLEANS

Orléans, France

Location

Institut Curie

Paris, 75005, France

Location

AP-HP Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Groupe Hospitalier Diaconesses-Croix Saint-Simon

Paris, 75020, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

Centre Hospitalier Général de Pau

Pau, 64046, France

Location

Centre CARIO - HPCA

Plérin, 22190, France

Location

CHU de Poitiers - Hôpital de la Milétrie

Poitiers, 86021, France

Location

CHI de Cornouaille

Quimper, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

CHU Saint-Etienne - Pôle de Cancérologie

Saint-Etienne, 42055, France

Location

Centre Hospitalier Privé de Saint-Grégoire

Saint-Grégoire, 35760, France

Location

ICO - Centre René Gauducheau

Saint-Herblain, 44805, France

Location

Institut de Cancérologie de Strasbourg Europe - ICANS

Strasbourg, 67200, France

Location

CHU Strasbourg - Hôpital de Hautepierre

Strasbourg, France

Location

Oncopole Claudius Regaud - IUCT Oncopole

Toulouse, 31059, France

Location

CHU Bretonneau

Tours, France

Location

ICL - Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Centro di Riferimento Oncologico

Aviano, 3308, Italy

Location

IRCCS Istituto Oncologico Giovanni Paolo II

Bari, 70124, Italy

Location

Ospedale degli Infermi

Biella, 13875, Italy

Location

Spedali Civili-Università di Brescia

Brescia, 25123, Italy

Location

Ospedale Civile degli Infermi

Faenza, 48018, Italy

Location

Ospedale San Luca

Lucca, 55100, Italy

Location

Ospedale "Umberto I"

Lugo, 48022, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale "Santa Maria delle Croci"

Ravenna, 48121, Italy

Location

Policlinco Umberto I

Roma, 00161, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale

Udine, 33100, Italy

Location

Kurume University Hospital

Fukuoka, 830-0011, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

Location

The Cancer Institute Hospital Of JFCR

Kōtoku, 135-8550, Japan

Location

Saitama Medical University International Medical Center

Saitama, 350-1298, Japan

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

National University Hospital (NUH)

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore (NCCS)

Singapore, 169610, Singapore

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei Medical Center Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital General Universitario de Elche

Elche, Alicante, 30203, Spain

Location

Hospital Germans Trias i Pujol / ICO Badalona

Badalona, 08916, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario de León

León, 24008, Spain

Location

Hospital Universitario Son Espases

Palma, 07120, Spain

Location

Hospital Son Llátzer

Palma de Mallorca, 07198, Spain

Location

Hospital Clínico Universitario Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Queen Elizabeth Hospital

Birmingham, B15 2GW GB, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ GB, United Kingdom

Location

Western General Hospital

Edinburgh, EH42XU, United Kingdom

Location

University College London Hospital

London, NW1 2PG GB, United Kingdom

Location

Northampton General Hospital NHS Trust

Northampton, NN1 5BD GB, United Kingdom

Location

Royal Cornwall Hospital

Truro, 3LJ GB, United Kingdom

Location

Related Publications (2)

• Secord AA, Powell MA, McAlpine J. Molecular Characterization and Clinical Implications of Endometrial Cancer. Obstet Gynecol. 2025 Nov 1;146(5):660-671. doi: 10.1097/AOG.0000000000006080. Epub 2025 Sep 18.

  PMID: 40966692 DERIVED

• Cherifi F, Ray-Coquard I, Rubio MJ, Paoletti X, Lorusso D, Choi CH, Hasegawa K, Tan DSP, Hudson E, Davis A, Tognon G, Lheureux S, Vardar Key MA, Kurtz JE, Alexandre J, Joly F. DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients. Future Oncol. 2025 Jun;21(13):1613-1623. doi: 10.1080/14796694.2025.2496133. Epub 2025 May 5.

  PMID: 40323277 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Neoplasm Metastasis

Interventions

CP protocol; dostarlimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Florence JOLY, Pr

  Centre François Baclesse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: January 21, 2022
• Study Start: April 15, 2022
• Primary Completion: April 1, 2026
• Study Completion (Estimated): October 1, 2029
• Last Updated: December 4, 2025

Record last verified: 2025-09

Locations

ES (9); FR (54); SG (2); GB (6); NZ (1); JP (4); AU (2); KR (7); IT (14); CA (1)