TSR-042 + Radiation for Endometrial Cancer

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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with inoperable endometrial cancer have limited treatment options. PD-L1 expression is common in endometrial cancers and RT induces tumor and systemic changes that induce the immune system. The purpose of this trial is to evaluate anti-PD-1/PD-L1 axis therapy in conjunction of standard of care RT for patients with inoperable endometrial cancer in order to establish the safety and efficacy of inducing an anti-tumor immune response.

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.

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

Research shows that dostarlimab, an immune therapy drug, significantly lowers the risk of death in patients with advanced or recurrent endometrial cancer compared to other treatments. It also helps patients live longer without needing to stop the treatment, indicating it is effective and well-tolerated. ^{1 2 3 4 5}

Is the combination of TSR-042 (Dostarlimab) and radiation therapy safe for humans?

Dostarlimab (also known as TSR-042 or Jemperli) has been approved for use in humans for certain types of endometrial cancer, indicating it has passed safety evaluations for these conditions. While specific safety data for the combination with radiation therapy isn't detailed, Dostarlimab has been studied and used safely in various cancer treatments. ^{1 2 4 5 6}

What makes the drug Dostarlimab unique for treating endometrial cancer?

Dostarlimab is unique because it is an immune-checkpoint inhibitor that targets the PD-1 receptor, specifically designed for endometrial cancer with mismatch repair deficiency, which may make these cancers more responsive to this type of treatment. ^{1 2 4 5 6}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

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

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

Dostarlimab: First Approval. [2021]

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

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm. [2023]

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

Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. [2022]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]