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

18 Participants Needed

Trial Summary

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.

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

Research shows that Niraparib, when used alone, helps extend the time without cancer progression in ovarian cancer patients. Additionally, a study found that combining Niraparib with Dostarlimab was effective in treating a specific type of ovarian cancer that is resistant to certain chemotherapy. ^{1 2 3 4 5}

Is the combination of Niraparib and Dostarlimab safe for humans?

Niraparib has been shown to be generally safe for humans, with the main safety concern being myelosuppression (a decrease in bone marrow activity leading to fewer blood cells). Dostarlimab has been approved for use in certain cancers, indicating it has been evaluated for safety, but specific safety data for the combination of Niraparib and Dostarlimab is not provided. ^{1 4 5 6 7}

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

This drug combination is unique because it combines Niraparib, a drug that helps prevent cancer cells from repairing themselves, with Dostarlimab, which helps the immune system recognize and attack cancer cells. This dual approach targets cancer in two different ways, potentially improving treatment effectiveness. ^{1 4 6 8 9}

What is the purpose of this trial?

This phase IB trial evaluates the effect of niraparib and TSR-042 in treating patients with BRCA-mutated breast, pancreas, ovary, fallopian tube, or primary peritoneal cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as TSR-042, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and TSR-042 may kill more cancer cells.

Research Team

Elizabeth Swisher, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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 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-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) 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]

References

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

Pharmaceutical Approval Update. [2020]

2. United States 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. [2023]

3. United States 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). [2023]

4. Germany 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. [2019]

5. France pubmed.ncbi.nlm.nih.gov

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

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

Dostarlimab: First Approval. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. [2023]

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

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

9. England pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. [2023]