Niraparib + Dostarlimab for Endometrial Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Casey Cosgrove

Must not be taking: PARP inhibitors

Disqualifiers: MDS, AML, Uncontrolled hypertension, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well niraparib and dostarlimab work in treating patients with uterine serous carcinoma that has come back (after a period of improvement) (recurrent) and remains despite treatment (persistent). Niraparib belongs to a class of drugs called PARP inhibitors that prevent cancer cells from growing. Dostarlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Dostarlimab belongs to a class of drugs called PD-1 inhibitors that uses the patient's own immune system to treat cancer (immuno-therapy). Giving niraparib and dostarlimab may work better in treating patients with uterine serous carcinoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you may need to discuss your specific medications with the study team to ensure they don't interfere with the trial treatments.

What data supports the effectiveness of the drug combination of Niraparib and Dostarlimab for endometrial cancer?

Research shows that the combination of Niraparib and Dostarlimab has shown modest activity in treating recurrent endometrial cancer, with a clinical benefit rate of 31.8% and a median benefit duration of 6.8 months. Dostarlimab has also been approved for treating certain types of endometrial cancer based on its ability to shrink tumors. ^{1 2 3 4 5}

Is the combination of Niraparib and Dostarlimab safe for treating endometrial cancer?

In a clinical trial assessing Niraparib and Dostarlimab for recurrent endometrial cancer, no new safety concerns were identified, suggesting that the combination is generally safe for use in humans. ^{1 2 3 4 5}

What makes the drug combination of Niraparib and Dostarlimab unique for endometrial cancer?

The combination of Niraparib and Dostarlimab is unique because it pairs a PARP inhibitor (Niraparib) with an immune-checkpoint inhibitor (Dostarlimab), potentially offering a synergistic effect for treating endometrial cancer, especially in patients with specific genetic profiles like mismatch repair deficiency. This approach is novel as there is no clear standard treatment for advanced or recurrent endometrial cancer after initial therapies. ^{1 2 3 5 6}

Research Team

Casey Cosgrove, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with recurrent or persistent uterine serous carcinoma who've had carboplatin/paclitaxel treatment. They should have an ECOG status of <=1, measurable disease by RECIST, and no more than three prior chemo regimens. Prior immunotherapy is allowed if there was no progression/toxicity leading to discontinuation. Participants must not be in other trials, haven't had major surgery within 3 weeks, and recovered from previous treatments' effects.

Inclusion Criteria

Absolute neutrophil count >= 1,500/uL

Patient must have measurable disease by RECIST

My blood clotting time is normal or managed with medication.

Exclusion Criteria

I have had PRES in the past.

Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients

I have had severe blood-related side effects from my last chemotherapy that lasted more than 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab intravenously and niraparib orally. They also undergo MRI/CT and collection of blood samples throughout the trial.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for 2 years and then annually.

2 years

Treatment Details

Interventions

• Dostarlimab
• Niraparib

Trial Overview The phase II trial tests niraparib (a PARP inhibitor that stops cancer cells from growing) combined with dostarlimab (a PD-1 inhibitor immuno-therapy). The study aims to see if this combination works better for treating patients with uterine serous carcinoma compared to current standard treatments.

Participant Groups

Group I: Treatment (dostarlimab, niraparib) Experimental Treatment 5 Interventions

Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.

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?

Casey Cosgrove

Lead Sponsor

Trials

1

Recruited

8+

Findings from Research

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]

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-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]

Dostarlimab demonstrated superior overall survival (OS) compared to doxorubicin in patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent endometrial cancer, with median OS not reached for dostarlimab versus 11.2 months for doxorubicin.

Dostarlimab also showed a better safety profile, with lower rates of grade ≥3 adverse events (48.1% for dostarlimab vs 78.3% for doxorubicin), indicating it may be a safer option for patients following platinum-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer. Mathews, C., Lorusso, D., Coleman, RL., et al.[2023]

References

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

Dostarlimab: First Approval. [2021]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma. [2023]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

6. England pubmed.ncbi.nlm.nih.gov

An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer. [2023]