Radiation + Dostarlimab for Endometrial Cancer

Recruiting at6 trial locations

Overseen by Ying Liu, MD, MPH

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-CTLA-4, Immunosuppressants

Disqualifiers: Prior chemotherapy, Active TB, Autoimmune disorders, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if combining radiation and Dostarlimab can effectively treat women with a specific type of endometrial cancer after surgery.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any other form of immunosuppressive therapy, you must stop these at least 7 days before the trial, unless it's a low dose or inhaled corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug dostarlimab for endometrial cancer?

Dostarlimab has been approved for treating adults with certain types of endometrial cancer based on its ability to shrink tumors and maintain this response over time. It has shown promising results in clinical trials, including a 100% remission rate in a trial for rectal cancer, suggesting its potential effectiveness in other cancers as well. ^{1 2 3 4 5}

Is the combination of radiation and dostarlimab safe for treating endometrial cancer?

Dostarlimab has been approved for use in certain types of endometrial cancer and other solid tumors, with safety data primarily coming from trials like the GARNET trial. While specific safety data for the combination with radiation isn't detailed, dostarlimab alone has been shown to be a potent and generally safe treatment option for advanced cancers. ^{1 2 3 4 6}

What makes the drug dostarlimab unique for treating endometrial cancer?

Dostarlimab is unique because it is a PD-1 monoclonal antibody that targets specific genetic features in endometrial cancer, particularly in patients with mismatch repair deficiencies. This targeted approach can lead to significant tumor response and has shown promising results in other cancers, like rectal cancer, indicating its potential for broader applications. ^{1 2 3 4 7}

Research Team

Ying Liu, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for women aged 18+ with MMR-D/MSI-H endometrial cancer who've had surgery. They must be in good health, not pregnant, agree to contraception, and have no severe allergies to Dostarlimab or its components. Exclusions include prior pelvic radiation, immune-related thyroidectomy in remission, certain autoimmune diseases unless approved by the study PI.

Inclusion Criteria

I am fully active or can carry out light work.

I have leftover cancer after surgery, but no cancer in my abdomen lining.

I am 18 years old or older.

Exclusion Criteria

Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

I cannot undergo radiation therapy due to certain health conditions.

Has psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Treatment

Participants undergo standard intensity modulated radiation therapy (IMRT) and receive Dostarlimab

5-6 weeks

Radiation therapy sessions and 4 cycles of Dostarlimab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Dostarlimab (PD-L1 Inhibitor)
• Intensity modulated radiation therapy (IMRT) (Radiation)

Trial Overview The effectiveness of combining radiation therapy (IMRT) with a drug called Dostarlimab is being tested on women with specific genetic types of endometrial cancer post-surgery. The goal is to see if this combination improves treatment outcomes compared to what's currently available.

Participant Groups

Group I: Radiation and Dostarlimab (THIS ARM IS COMPLETED) Experimental Treatment 2 Interventions

Patients will undergo standard intensity modulated radiation therapy (IMRT) to the pelvic nodes and vaginal cuff (total dose of 45-50.4Gy at 1.8 Gy per fraction) for 5-6 weeks and receive IV Dostarlimab every 3 weeks for 4 cycles followed by 1 dose of 1000mg (C5). Patients will receive a maximum of 5 cycles of Dostarlimab.

Group II: Hypofractionated IMRT and Dostarlimab Experimental Treatment 2 Interventions

Treatment will consist of short-course, hypofractionated IMRT to deliver 25 Gy to the vaginal cuff and pelvic lymph nodes in 5 daily fractions over one week. Participants will receive TSR-042 500mg every 3 weeks over 30 minutes for 4 cycles, followed by 1 dose of 1000mg for cycle 5.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Findings from Research

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

Dostarlimab showed significant antitumor activity in patients with advanced endometrial cancer, achieving an objective response rate (ORR) of 43.5% in those with dMMR/MSI-H disease, compared to 14.1% in those with proficient/stable disease, indicating its potential effectiveness in specific cancer subtypes.

The treatment had a manageable safety profile, with most adverse events being mild to moderate (grade 1-2), and no deaths attributed to the drug, suggesting it is a safe option for patients with advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. Oaknin, A., Gilbert, L., Tinker, AV., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Real-world dostarlimab use in advanced/recurrent endometrial cancer in France. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. [2022]