TSR-042 + Radiation for Endometrial Cancer

Not currently recruiting at 1 trial location

Overseen By Stephanie Markovina, M.D., Ph.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Chemotherapy, Immunosuppressants, others

Disqualifiers: Metastatic disease, Other malignancy, others

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

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

Compensation: Varies

Number of Visits: 42

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with early-stage endometrial cancer that cannot be surgically removed. It combines the drug TSR-042 (also known as Dostarlimab or Jemperli) with radiation therapy to determine if this combination can safely activate the immune system to combat the cancer. The trial suits those newly diagnosed with specific types of endometrial cancer who cannot undergo surgery and are candidates for radiation therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 corticosteroids, you can continue as long as your dose is stable for at least 4 weeks before starting the trial.

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

Research has shown that TSR-042, also known as dostarlimab, is generally safe for patients with advanced endometrial cancer. When combined with chemotherapy, it can effectively slow disease progression without causing severe issues. Real-world reports also support its safety, indicating that patients tolerate the drug well.

Brachytherapy, a type of radiation treatment, has proven safe for patients with inoperable cancers. One study found that it stopped vaginal bleeding in 83% of patients, suggesting it is a safe and effective way to manage symptoms.

Both TSR-042 and brachytherapy have demonstrated safety in other studies, offering hope for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

TSR-042 is unique because it leverages the power of immunotherapy, specifically a PD-1 inhibitor, to enhance the body's own immune response against endometrial cancer. Unlike traditional treatments like surgery, chemotherapy, or external beam radiation, TSR-042 is combined with brachytherapy, a type of internal radiation, to potentially improve targeting of cancer cells while minimizing damage to surrounding healthy tissues. Researchers are excited about this treatment because it offers a new approach that might increase effectiveness and reduce side effects, promising a more tailored and potentially more effective option for patients with endometrial cancer.

What evidence suggests that TSR-042 and brachytherapy could be effective for inoperable endometrial cancer?

Research has shown that TSR-042, also known as dostarlimab, holds promise for treating endometrial cancer. One study significantly extended the time patients with advanced or returning cancer lived without disease progression. Another study found it reduced the risk of death, with patients more than twice as likely to survive compared to those not receiving the treatment.

Brachytherapy, a type of targeted radiation therapy, has also proven effective. It increased the 3-year survival rate by 5% for patients with stage III endometrial cancer and stopped vaginal bleeding in 83% of patients unable to undergo surgery. In this trial, participants will receive a combination of TSR-042 and brachytherapy, aiming to harness both immune and radiation benefits, offering strong potential for treating inoperable endometrial cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephanie Markovina, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with inoperable endometrial cancer who can undergo radiation therapy. They must have adequate organ function, not be pregnant or breastfeeding, and agree to use contraception if of childbearing potential. Excluded are those with prior endometrial cancer treatments, metastatic disease outside the uterus, certain recent malignancies, previous anti-PD-1/PD-L1 drugs usage, known brain metastases, uncontrolled medical conditions or infections.

Inclusion Criteria

Platelets ≥ 100,000/µL

I agree not to donate blood during and for 3 months after the study.

My organs are functioning well.

Exclusion Criteria

I do not have brain or spinal cord cancer spread.

I have an autoimmune disease treated with strong medication in the last 2 years.

I do not have any serious health issues that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four doses of TSR-042 in conjunction with six weekly fractions of brachytherapy

9 weeks

Weekly visits for brachytherapy and TSR-042 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• TSR-042

Trial Overview The trial tests TSR-042 (an immunotherapy drug) alongside standard radiation treatment for patients with inoperable endometrial cancer. It aims to assess whether adding TSR-042 can boost the immune system's response against tumor cells and improve outcomes compared to radiation alone.

How Is the Trial Designed?

Group I: TSR-042 and Brachytherapy Experimental Treatment 4 Interventions

* Patients will receive four doses of TSR-042. The first dose is given 21 days prior to the first planned brachytherapy fraction. The second dose is given 21 (+3) days later, corresponding to the time of brachytherapy fraction #1. The third dose is given 21 (+3) days after dose 2, corresponding to the time of brachytherapy fraction #4. The fourth dose is given 21 (+3) days after dose corresponding to 1 weeks after brachytherapy fraction #6. * Brachytherapy will consist of 6 weekly fractions of 6 Gy per fraction (total 36Gy)

TSR-042 is already approved in United States, European Union for the following indications:

Approved in United States as Jemperli for:

• Endometrial cancer (dMMR/MSI-H)
• Primary advanced or recurrent endometrial cancer

Approved in European Union as Jemperli for:

• Endometrial cancer (dMMR/MSI-H)
• Primary advanced or recurrent endometrial cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

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-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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10863227/

Review of brachytherapy clinical trials - PubMed Central - NIH Brachytherapy is a form of highly conformal radiotherapy that involves implantation of radiation sources into or near a target tumor using ...

2. healthcare.utah.edu healthcare.utah.edu/huntsmancancerinstitute/press-releases/2025/02/short-course-radiation-therapy-effective-endometrial-cancer-patients

Short-Course Radiation Therapy Effective for Endometrial ... Short-course, higher dose vaginal brachytherapy for endometrial cancer had similar effectiveness to more frequent, lower dose sessions.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1538472121000441

Role of brachytherapy in stage III endometrial cancer ... In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in ...

4. mdpi.com mdpi.com/2075-4426/14/12/1138

Safety and Efficacy of Brachytherapy in Inoperable ... Despite these weaknesses, our clinical results are promising. Vaginal bleeding stopped in 83% of patients, and the recurrence rate was 33.3%. It is important to ...

5. cancerindex.org cancerindex.org/Brachytherapy

Brachytherapy This study evaluates the survival and pain relief outcomes of the I-seeds implantation brachytherapy in advanced pancreatic cancer patients.

6. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)04483-4/abstract

Salvage brachytherapy for local recurrence of cancer after ... Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer.

7. mayoclinic.org mayoclinic.org/tests-procedures/brachytherapy/about/pac-20385159

Brachytherapy The overall treatment time can be shorter with brachytherapy because a larger dose of radiation can be safely delivered at one time. Why it's ...