Clinical Trial to Assess the Efficacy of Dostarlimab as Neoadjuvant Therapy in Patients With MMRd/MSI-H Stage II-III Endometrial Cancer

NCT07013851 | Not Yet Recruiting Phase 2

• 2 other identifiers: GEICO 137-E2024-512021-81-00
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The study for which participation is requested is a phase II clinical trial to assess the efficacy of dostarlimab as neoadjuvant therapy in patients with MMRd/MSI-H stage II-III endometrial cancer. The study is conducted in Spain with an estimated number of 25 patients for phase II. The main objective of this phase-II study is to evaluate the clinical complete response (cCR) after neoadjuvant therapy with dostarlimab.

Conditions

MMRd/MSI-H Stage II-III Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the clinical complete response (cCR) after neoadjuvant dostarlimab.

  cCR: Efficacy measured by the proportion of patients who had cCR after neoadjuvant dostarlimab. cCR is defined as the absence of tumor persistence evaluated by MRI, CT, PET scan, pelvic exam, and review of surgical specimen.

  43 months

Secondary Outcomes (5)

• To evaluate the pathologic complete response (pCR) after neoadjuvant dostarlimab.

  51 months

• To evaluate the overall response rate (ORR) of neoadjuvant dostarlimab.

  51 months

• To evaluate disease-free survival (DFS).

  51 months

• To evaluate the median of overall survival (mOS).

  51 months

• To evaluate the safety and tolerability of dostarlimab in the neoadjuvant setting.

  51 months

Study Arms (1)

1

EXPERIMENTAL

Patients will be treated in the neoadjuvant setting with dostarlima 500 mg (30') every 3 weeks for 4 cycles.All participants will undergo surgery within 6 weeks following the final dose of neoadjuvant dostarlimab. After surgery, adjuvant chemotherapy, including dostarlimab, will be administered as follows: Stage II EC: VBT/EBRT (completed within \>14 weeks after surgery) + Adjuvant dostarlimab 1000 mg Q6W x 9 cycles (54 weeks total). Stage III EC: 1. Concurrent EBRT+cisplatin followed by carboplatin + paclitaxel OR 2. Sequential: EBRT followed by carboplatin + paclitaxel OR 3. Chemotherapy alone: carboplatin + paclitaxel * Adjuvant dostarlimab 500 mg Q3W x 4-6 cycles (in combination with chemotherapy) plus 1000 mg Q6W x 6-7 cycles (54 weeks total).

Drug: Dostarlimab

Interventions

Dostarlimab DRUG

Patients will be treated in the neoadjuvant setting with dostarlima 500 mg (30') every 3 weeks for 4 cycles.All participants will undergo surgery within 6 weeks following the final dose of neoadjuvant dostarlimab. After surgery, adjuvant chemotherapy, including dostarlimab, will be administered as follows: Stage II EC: VBT/EBRT (completed within \>14 weeks after surgery) + Adjuvant dostarlimab 1000 mg Q6W x 9 cycles (54 weeks total). Stage III EC: 1. Concurrent EBRT+cisplatin followed by carboplatin + paclitaxel OR 2. Sequential: EBRT followed by carboplatin + paclitaxel OR 3. Chemotherapy alone: carboplatin + paclitaxel * Adjuvant dostarlimab 500 mg Q3W x 4-6 cycles (in combination with chemotherapy) plus 1000 mg Q6W x 6-7 cycles (54 weeks total).

1

Eligibility Criteria

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

You may qualify if:

• Female subjects at least 18 years of age, who are able to understand the study procedures and agree to participate in the study by providing written informed consent.
• Histologically confirmed new diagnosis of endometrial adenocarcinoma (endometrioid subtype only) by central pathology review.
• MMRd status confirmed by IHC by central laboratory.
• Subject must provide adequate tumor tissue sample at screening for MMR/MSI status testing. The quality of the tumor tissue sample must be confirmed by the central laboratory during screening.
• Subjects must have primary stage II or III (FIGO 2023) disease. Pelvic involvement is included. Stage IIIB2 patients with metastasis to pelvic peritoneum are excluded.
• ECOG performance status of 0 or 1.
• Treatment naïve patients without previous radiation or systemic therapy, including hormonal therapy.
• Participants should have adequate organ function defined as:
• ANC ≥1.5×109/L
• Hemoglobin ≥9 g/dL ≥5.6 mmol/L
• Platelets ≥100×109/L
• AST and ALT ≤2.5×ULN
• Bilirubin ≤1.5×ULN (isolated bilirubin \>1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%)
• For patients not taking anticoagulant: INR ≤ 1.5x or PT ≤1.5× ULN. Activated partial thromboplastin time (aPTT) ≤1.5× ULN. Participants receiving anticoagulants PT or PTT are within therapeutic range of intended use of anticoagulants.
• Renal function parameters of GFR ≥30 mL/min/1.73m2 (institutional creatinine ≤1.5×ULN) Note: Blood count test should be performed without transfusion or receipt of colony stimulating factors within 4 weeks prior to obtaining the blood sample.

You may not qualify if:

• Diagnosis of clear cell, serous, undifferentiated or carcinosarcoma or other uterine mesenchymal tumor such as endometrial stromal sarcoma, leiomyosarcoma, or other types of sarcomas. Adenosarcomas and neuroendocrine tumors are not allowed either.
• Any previous radiation or systemic therapy.
• ECOG performance status ≥2.
• Immunodeficiency or treatment with chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy.
• Subject has a concomitant malignancy, or 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.
• Participants have current active or history of pneumonitis or interstitial lung disease.
• Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
• Immunocompromised patients are not allowed.
• Allergy: Participant cannot have history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins, sensitivity to any of the study treatments or components thereof, or a history of drug or other allergy that contraindicates their participation.
• Participant has clinically significant cardiovascular disease within 6 months of enrolment.
• Prohibited medications: Participant has received systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 7 days before the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy (adrenal or pituitary insufficiency) is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
• Subject has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
• Subject has known active hepatitis B. Participants who are HBsAg positive are eligible if they have undetectable HBV viral load prior to enrolment.
• Subject has a positive HCV antibody test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is obtained.

Sponsors & Collaborators

• Grupo Español de Investigación en Cáncer de Ovario: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Grupo Español de Investigación en Cáncer Ginecológico (GEICO)

Madrid, Madrid, 28003, Spain

Location

MeSH Terms

Interventions

dostarlimab

Central Study Contacts

Grupo Español de Investigación en Cáncer Ginecológico

CONTACT

+34 910 09 72 58; secretaria@grupogeico.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 10, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)