Evaluating dostarlimab for advanced endometrial cancer

A Retrospective, Real-world Multicenter Study of DOstarlimab in Patients With Recurrent or Advanced DNA Mismatch Repair Deficient/Microsatellite Instability-high (dMMR/MSI-H) Endometrial Cancer (DORA Study)

This study is testing if a new drug called dostarlimab can help people with advanced endometrial cancer that hasn't responded to previous treatments.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years to 100 Years
• Sex: Female
• Sponsor: Grupo Español de Investigación en Cáncer de Ovario (other)
• Drugs / interventions: dostarlimab, chemotherapy, immunotherapy
• Locations: 1 site (Valencia, Comunidad Valenciana)
• Trial ID: NCT05728814 on ClinicalTrials.gov

What this trial studies

This multicenter, retrospective observational study aims to assess the effectiveness of dostarlimab in patients with recurrent or advanced endometrial cancer characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). Conducted across 50-60 hospitals in Spain, the study will include approximately 110 patients who have progressed after platinum-based chemotherapy. The primary objective is to evaluate the antitumor activity of dostarlimab, while secondary objectives include assessing progression-free survival, overall survival, and safety. Patient eligibility will be determined through medical record screening by local clinical staff.

Who should consider this trial

Good fit: Ideal candidates are adults with recurrent or advanced dMMR/MSI-H endometrial cancer who have progressed after platinum-based chemotherapy.

Not a fit: Patients with endometrial sarcoma or those who have not received prior platinum-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced endometrial cancer who have limited therapeutic alternatives.

How similar studies have performed: Other studies have shown promising results with dostarlimab in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age, able to understand the program procedures and agree to participate by providing written informed consent.
2. Histologically diagnosed endometrial cancer (note: all histologies are permitted except endometrial sarcoma \[including carcinosarcoma\]).
3. Patient has evidence of tumor DNA damage repair dysfunction (dMMR/MSI-H) via locally available, validated methodology.
4. Patient has progressed on or after platinum containing chemotherapy (and has received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage ≥ IIIB) disease (first or second line)); prior treatment with hormone therapies is acceptable and does not count towards the number of lines of therapy.
5. ECOG performance status of ≤ 2.
6. Adequate organ and bone marrow function, as defined below:

   1. Absolute neutrophil count (ANC) ≥ 1,500/µL
   2. Platelets ≥ 100,000/µL
   3. Hemoglobin ≥ 9 g/dL
   4. Adequate liver and renal function:

      * Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine levels \> 1.5 × institutional ULN.
      * Total bilirubin ≤ 1.5 × ULN AND direct bilirubin ≤ 1 × ULN.
      * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case they must be ≤ 5 × ULN.
7. Cannot be satisfactorily treated with available alternative treatments.
8. Not eligible for a clinical trial with dostarlimab within the indication of the EAP (where access to the clinical trialsite is possible)
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and if one of the following conditions applies:

   * Is a woman of non-childbearing potential (WONCBP) OR
   * Is a WOCBP and using a contraceptive method that is highly effective (with a failurerate of \< 1 % per year), preferably with low user dependency, during treatment and for at least 4 months after treatment. The treating physician should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated)in relationship to the first doseof dostarlimab.

A WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours before the first dose of dostarlimab. The treating physician is responsible for review of medical history, menstrual history, andrecent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy

Exclusion Criteria:

1. Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
2. Is considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease, or active infection requiring antibiotic, antifungal or antiviral treatment.
3. Has undergone major surgery 3 weeks prior to initiating dostarlimab (and not recovered from surgical effects).
4. Has malignancies other than endometrial cancer (except for any other malignancy for which the patient is not being actively treated).
5. Has a history of interstitial lung disease.
6. Has an active autoimmune disease that required systemic treatment in the past 2 years (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
7. Has experienced ≥ Grade 3 immune related AE with prior immunotherapy, except for non-clinically significant laboratory abnormalities.
8. Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected).
9. Has received a live vaccine within 14 days of 1st dose of dostarlimab.
10. Has a known hypersensitivity to dostarlimab components or excipients

Where this trial is running

Valencia, Comunidad Valenciana

• Hospital Arnau de Vilanova — Valencia, Comunidad Valenciana, Spain (RECRUITING)

Study contacts

• Principal investigator: Alejandro Gallego Martinez — Clinica Universitaria de Navarra
• Study coordinator: Patricio Ledesma

Conditions: Endometrial Cancer