Radiation + Dostarlimab for Endometrial Cancer

Recruiting at 6 trial locations

Overseen By Roisin O'Cearbhaill, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining radiation with Dostarlimab can effectively treat a specific type of endometrial cancer with certain genetic characteristics (MMR-D/MSI-H). It targets women who have undergone surgery for their cancer but require further treatment. Participants will receive either a standard or shorter course of radiation along with Dostarlimab, administered through an IV. Women who have had surgery for stage III/IVA endometrial cancer and possess specific genetic markers may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Dostarlimab is generally well-tolerated by patients. When combined with chemotherapy, it extends the lives of those with advanced endometrial cancer. Common side effects, affecting 10% or more of patients, include fatigue and nausea. However, studies conducted over two years indicate that serious side effects are uncommon.

Intensity-Modulated Radiation Therapy (IMRT) is also considered safe for patients with endometrial cancer. It causes fewer gastrointestinal issues, such as diarrhea, compared to older radiation methods. For instance, only 11% of patients experienced significant digestive problems with IMRT, compared to 19.2% with other treatments.

Together, Dostarlimab and IMRT offer promising safety outcomes for patients interested in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dostarlimab for endometrial cancer because it offers a new approach compared to traditional treatments like surgery, chemotherapy, or radiation alone. Dostarlimab is a type of immunotherapy that works by blocking PD-1, a protein that tumors use to hide from the immune system, thereby helping the body to better recognize and attack cancer cells. Additionally, when combined with hypofractionated radiation, which involves fewer but higher doses of radiation over a shorter period, this approach might provide a quicker, more effective treatment option with potentially fewer side effects. This combination aims to enhance the body's immune response against the cancer, offering hope for improved outcomes in patients with endometrial cancer.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

This trial will compare two treatment approaches for endometrial cancer. One arm involves standard Intensity Modulated Radiation Therapy (IMRT) combined with Dostarlimab, while the other uses a faster form called hypofractionated IMRT with Dostarlimab. Studies have shown that Dostarlimab significantly slows the growth and spread of endometrial cancer. For patients with certain biomarkers (dMMR/MSI-H), it effectively delayed cancer progression for an average of 30 months. Research indicates that Dostarlimab can shrink or even eliminate tumors in many women. Radiation therapy, like IMRT, reduces side effects on healthy tissues while effectively treating cancer. Hypofractionated IMRT, part of one trial arm, has shown high success rates in controlling the disease and is easier on the body. Together, these treatments offer promising results for managing endometrial cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Ying Liu, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Intensity modulated radiation therapy (IMRT)

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.

How Is the Trial Designed?

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. For this group, in those patients who have delays in C2 of dostarlimab and/or are unable to receive the 2nd dose of dostarlimab, hypofractionated radiation may proceed independently per discretion of treating investigator in consultation with study PI.

Dostarlimab is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

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]

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 (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]

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, a programmed death-1 inhibitor, was granted early access in France and showed a disease control rate of 56% and an overall response rate of 35% in patients with advanced endometrial cancer, consistent with results from the GARNET trial.

No new safety concerns were identified during the real-world use of dostarlimab in 80 patients, indicating that it is a safe option for those who have limited treatment options after platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world dostarlimab use in advanced/recurrent endometrial cancer in France. Rodrigues, M., Eberst, L., Follana, P., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2216334

Dostarlimab for Primary Advanced or Recurrent ... Dostarlimab plus carboplatin–paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer.

2. jemperli.com jemperli.com/endometrial-cancer/

Results for JEMPERLI | JEMPERLI (dostarlimab-gxly) People with dMMR/MSI-H biomarker status taking JEMPERLI + CP experienced a median of 30 months without their cancer growing, spreading, or getting worse. The ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37620100/

data from the GARNET trial and the National Cancer ... For all three scenarios, progression-free survival rates at 12 and 18 months were higher for patients on dostarlimab compared with the real- ...

4. onclive.com onclive.com/view/real-world-analysis-confirms-efficacy-safety-of-dostarlimab-plus-chemotherapy-in-advanced-endometrial-cancer

Real-World Analysis Confirms Efficacy/Safety of ... Dostarlimab-gxly with carboplatin and paclitaxel shows comparable PFS in real-world settings and the RUBY trial for advanced endometrial cancer.

5. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/jemperli

Jemperli | European Medicines Agency (EMA) At follow up after at least 24 weeks, the cancer had shrunk or could no longer be detected in 43.5% of women receiving Jemperli. Further data from the study ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39346117/

Safety of dostarlimab in combination with chemotherapy ... Dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone.

7. jemperlihcp.com jemperlihcp.com/safety-profile/garnet-trial/

GARNET Safety Profile | JEMPERLI (dostarlimab-gxly) Safety Outcomes for JEMPERLI Monotherapy From the GARNET Trial. Safety profile established over more than 2 years 1. Adverse reactions (≥10%) in patients ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0090825824011727

Efficacy and safety of dostarlimab in combination with ... Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with ...

9. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06278857

NCT06278857 | SATELLITE Study (feaSibility sAfeTy ... The study aims to establish dostarlimab's efficacy and safety in early-stage endometrial cancer, exploring its potential as a non surgical option for those ...