Niraparib + Dostarlimab for Cancer

Overseen By Elizabeth M. Swisher

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: MDS, AML, Uncontrolled infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 30

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two drugs, niraparib and dostarlimab, can treat certain cancers with a BRCA gene mutation, especially when surgery cannot remove the cancer or it has spread. Niraparib, a PARP inhibitor, stops cancer cells from repairing damaged DNA, while dostarlimab, an immunotherapy drug, helps the immune system fight cancer. The trial seeks participants with specific cancers such as breast, pancreas, ovary, fallopian tube, or primary peritoneal cancer who have not succeeded with other treatments. Participants should be willing to undergo biopsies and able to take oral medications. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative 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, certain treatments like recent investigational therapies, radiation, or transfusions have specific time restrictions before starting the trial. It's best to discuss your current medications with the trial team to get personalized advice.

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

Research has shown that combining the drugs niraparib and dostarlimab is generally safe for patients. In a study on ovarian cancer, researchers identified no major safety concerns with this combination, indicating it is well-tolerated. Another study found that using dostarlimab with other treatments also did not cause significant safety issues.

While some people might experience side effects, research so far indicates these are not severe for most patients. The absence of major safety problems in previous studies is encouraging for those considering joining a clinical trial with these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about niraparib combined with dostarlimab because it offers a fresh approach to cancer treatment. Unlike traditional therapies that might focus solely on chemotherapy or radiation, this combination uses niraparib, a PARP inhibitor that disrupts cancer cell repair mechanisms, and dostarlimab, an immunotherapy that helps the immune system better recognize and attack cancer cells. This dual-action strategy has the potential not only to directly damage cancer cells but also to enhance the body's natural defenses against them, which could lead to more effective and lasting treatment outcomes.

What evidence suggests that niraparib and dostarlimab might be effective treatments for BRCA-mutated cancer?

Research has shown that using niraparib and dostarlimab together can help treat certain cancers. In this trial, participants will receive both niraparib and dostarlimab. Niraparib inhibits a protein called PARP, which cancer cells use to repair damaged DNA. By blocking this repair, cancer cells can die. Dostarlimab boosts the immune system to find and attack cancer cells. Earlier studies demonstrated that this combination helped patients with ovarian cancer live longer without their cancer worsening. Although more information is still being gathered, these findings suggest possible benefits for patients with BRCA-mutated cancers. ^{1 4 5 6 7}

Who Is on the Research Team?

Elizabeth Swisher, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with certain types of cancer (breast, pancreas, ovary, fallopian tube, or primary peritoneal) that can't be surgically removed or has spread and have a BRCA mutation. They must have acceptable blood counts and organ function, agree to contraception if applicable, not breastfeed during the trial period, and could undergo biopsies. Excluded are those with recent major surgeries or therapies, active infections or other serious health issues.

Inclusion Criteria

My brain metastases are stable, not bleeding, and I haven't needed steroids or seizure meds for over a week.

I am not pregnant, can avoid pregnancy, or cannot become pregnant.

I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

I have not received a live vaccine in the last 14 days.

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

I had a severe reaction to previous immunotherapy, except for minor lab changes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally once daily and dostarlimab intravenously, with cycles repeating every 21 days for 4 cycles, then every 42 days for up to 24 months

24 months

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

30 days post-treatment, then every 6 months for 2 years, and annually up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• TSR-042

Trial Overview The trial is testing niraparib (a PARP inhibitor that stops cancer cells from repairing their DNA) combined with TSR-042 (an immunotherapy drug). The goal is to see if this combination helps the immune system fight cancer better and prevents tumor growth in patients with specific advanced cancers.

How Is the Trial Designed?

Group I: Treatment (niraparib, dostarlimab) Experimental Treatment 6 Interventions

Patients receive niraparib PO QD on days 1-28 of cycle 1. Beginning cycle 2, patients receive niraparib PO QD on days 1-21 and dostarlimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 6, patients receive niraparib PO QD on days 1-42 and dostarlimab IV over 30 minutes on day 1. Cycles repeat every 42 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy, blood sample collection, and CT or MRI throughout the study.

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

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase III trial involving patients with advanced breast cancer and germline BRCA1/2 mutations, niraparib showed a median progression-free survival (PFS) of 4.1 months compared to 3.1 months for physician's choice chemotherapy, although the difference was not statistically significant (P = 0.86).

Despite the trial being halted due to issues with data assessment, niraparib demonstrated a 35% objective response rate, indicating its potential effectiveness in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study. Turner, NC., Balmaña, J., Poncet, C., et al.[2023]

The combination treatment of dostarlimab and niraparib in patients with recurrent platinum-resistant ovarian cancer showed a low objective response rate of only 7.3%, leading to the early termination of the study due to insufficient efficacy.

Despite the treatment being generally safe with no new safety issues identified, 95.1% of patients experienced treatment-related adverse events, and health-related quality of life worsened over time, indicating a need for more effective therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Randall, LM., O'Malley, DM., Monk, BJ., et al.[2023]

In a study of 94 patients with non-gBRCA1/2 mutated recurrent ovarian cancer, niraparib maintenance treatment demonstrated effectiveness similar to phase III trials, with a median time to first subsequent treatment of 10.7 months.

Individualized dosing based on patient weight and platelet counts led to fewer dose reductions and interruptions, highlighting the importance of personalized treatment to enhance safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. Vilming, B., Fallås Dahl, J., Bentzen, AG., 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]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Niraparib (Zejula) is effective for treating recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, providing a targeted therapy option for these specific cancer types.

Ocrelizumab (Ocrevus) has shown efficacy in managing both relapsing and primary progressive multiple sclerosis, while dupilumab (Dupixent) is effective for patients with moderate-to-severe atopic dermatitis, highlighting its role in managing chronic inflammatory skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Dostarlimab (JEMPERLI) has been shown to effectively reduce tumor size in patients with certain types of endometrial cancer, as demonstrated in the ongoing GARNET phase 1 clinical study.

The treatment was associated with manageable side effects and few severe adverse reactions, leading to its approval for patients with advanced or recurrent endometrial cancer, where treatment options are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. Oaknin, A., Gilbert, L., Tinker, AV., 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40377969/

Phase II Study Evaluating the Efficacy of Niraparib and ... At a median follow-up of 10.13 months, the median progression-free survival was 3.8 months, and the median overall survival was 10.1 months. The ...

2. aacrjournals.org aacrjournals.org/cancerrescommun/article/doi/10.1158/2767-9764.CRC-25-0192/762454/am/Phase-II-study-evaluating-the-efficacy-of

Phase II study evaluating the efficacy of niraparib and ... Phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03955471

NCT03955471 | Study to Evaluate the Efficacy and Safety ... This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants ...

4. cancernetwork.com cancernetwork.com/view/dostarlimab-chemo-maintenance-niraparib-show-modest-improvements-in-ovarian-cancer

Dostarlimab/Chemo, Maintenance Niraparib Show Modest ... The median PFS with dostarlimab plus niraparib was 20.6 months vs 19.2 months with niraparib alone in patients with treatment-naive advanced ovarian cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA5506

FIRST/ENGOT-OV44: A phase 3 clinical trial of dostarlimab ... Niraparib efficacy and safety in patients with BRCA mutated (BRCAm) ovarian cancer: Results from three phase 3 niraparib trials. Antonio ...

6. targetedonc.com targetedonc.com/view/first-trial-no-safety-interaction-between-dostarlimab-and-niraparib

FIRST Trial: No Safety Interaction Between Dostarlimab ... A recent trial evaluates the impact of dostarlimab on ovarian cancer treatment, revealing modest benefits and no significant safety concerns ...

7. 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.