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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, niraparib and dostarlimab, in treating uterine serous carcinoma. Niraparib aims to stop cancer cell growth, while dostarlimab (also known as Jemperli) boosts the immune system to fight the cancer. The trial targets individuals whose cancer has returned or persists after treatment and who have already tried chemotherapy drugs like carboplatin and paclitaxel. Participants must have tumor tissue available and be able to take oral medications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective therapy.

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.

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

Research shows that the combination of dostarlimab and niraparib is being tested for safety in treating endometrial cancer. In similar studies, patients using this combination have shown improvements in controlling cancer growth. These studies also provide information about the safety of these treatments.

Patients taking dostarlimab have experienced some side effects, but these are often manageable. Common side effects include fatigue, nausea, and low blood cell counts. Niraparib, often used with dostarlimab, has similar side effects, such as tiredness and changes in blood counts.

While these treatments appear promising, it's important to note that the trial is in Phase 2. This phase focuses on understanding the safety and effectiveness of the treatment in a larger group. So far, the combination treatment has been fairly well-tolerated, with no unexpected safety issues.

Prospective participants should consult their healthcare provider to understand the benefits and risks based on their personal health situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining niraparib and dostarlimab for endometrial cancer because of their unique mechanisms of action. Unlike standard treatments, which often rely on chemotherapy and hormone therapy, niraparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death. Dostarlimab, on the other hand, is an immunotherapy drug that helps the immune system recognize and attack cancer cells by blocking the PD-1 pathway. This combination aims to both directly kill cancer cells and enhance the body's immune response, offering a potentially more effective and targeted treatment option for endometrial cancer patients.

What evidence suggests that niraparib and dostarlimab might be effective for endometrial cancer?

Research shows that combining niraparib with dostarlimab can help treat advanced or recurrent endometrial cancer. In this trial, participants will receive both medications. Studies have found that this combination significantly extends the time patients live without their cancer worsening. While niraparib alone didn't meet expectations, it proved more effective when paired with dostarlimab. Dostarlimab, a type of immunotherapy, helps the body's immune system fight cancer. Overall, this combination has shown promising results for patients with challenging cases of endometrial cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Casey Cosgrove, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. onclive.com onclive.com/view/dostarlimab-chemo-niraparib-generates-pfs-benefit-in-primary-recurrent-endometrial-cancer

Dostarlimab/Chemo/Niraparib Generates PFS Benefit in ... Dostarlimab plus chemotherapy followed by niraparib maintenance significantly improved PFS in advanced/recurrent endometrial cancer. Median PFS ...

2. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/6/939/762896/Phase-II-Study-Evaluating-the-Efficacy-of

Phase II Study Evaluating the Efficacy of Niraparib and ... We designed a single-arm, open-label, phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.

3. cancernetwork.com cancernetwork.com/view/dostarlimab-niraparib-improves-pfs-outcomes-in-advanced-endometrial-cancer

Dostarlimab/Niraparib Improves PFS Outcomes in ... The trial met its primary end point with a statistically significant, clinically meaningful improvement in PFS with the dostarlimab combination ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10017680/

Clinical outcome and biomarker assessments of a multi- ... In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03016338

NCT03016338 | Study of Niraparib and TSR-042 in ... This is a phase 2 study of investigational drug niraparib and TSR-042 in patients with advanced/recurrent endometrial cancer. The purpose of this study is ...

6. gsk.com gsk.com/en-gb/media/press-releases/jemperli-plus-zejula-combination-significantly-improved-progression-free-survival-in-endometrial-cancer-phase-iii-trial/

Jemperli (dostarlimab) plus Zejula (niraparib) combination ... Jemperli (dostarlimab) plus Zejula (niraparib) combination significantly improved progression-free survival in primary advanced or recurrent endometrial cancer.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36972026/

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

8. esmoopen.com esmoopen.com/article/S2059-7029(24)01307-3/fulltext

Results from part 2 of the RUBY trial 38MO Progression-free survival (PFS) in primary advanced or recurrent endometrial cancer (pA/rEC) in the overall and mismatch repair proficient (MMR/MSS) ...

9. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/phase-iii-trial-data-show-meaningful-survival-improvements-with-jemperli-combinations-for-endometrial-cancer

Phase III Trial Data Show Meaningful Survival ... Survival data from the Phase III RUBY/ENGOT-EN6/GOG3031/NSGO trial demonstrated statistically significant and clinically meaningful outcomes ...