Niraparib + Dostarlimab for Pancreatic Cancer

No longer recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: PARP inhibitors, Immunotherapy

Disqualifiers: Brain metastases, Active infection, Uncontrolled disease, 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: 33

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, niraparib and dostarlimab, to evaluate their effectiveness in treating pancreatic cancer that has spread. Niraparib blocks certain cell-growth enzymes to stop cancer cells from growing, while dostarlimab (also known as Jemperli) enhances the immune system's ability to fight cancer. Individuals with a specific gene mutation (BRCA1/2 or PALB2) who have already undergone one or two treatments for metastatic pancreatic cancer might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on certain treatments like chemotherapy, radiotherapy, or investigational drugs, you may need to stop or adjust them before joining the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of niraparib and dostarlimab is being tested for safety in other conditions, such as ovarian cancer. One study found no major safety issues when these two treatments were used together. Another study showed that patients tolerated the combination well, with no serious safety problems reported. While these results are encouraging, safety can vary depending on the condition being treated. It is important to consult a healthcare provider about any personal concerns or questions before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which often involve chemotherapy or radiation, this new combination of niraparib and dostarlimab offers a unique approach. Niraparib is a PARP inhibitor, which targets cancer cells by preventing them from repairing their DNA, while dostarlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. Researchers are excited because this dual-action strategy not only disrupts cancer cell repair but also enhances the body's natural defenses, potentially offering a more powerful and targeted attack against pancreatic cancer.

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

Research has shown that using niraparib and dostarlimab together may help treat pancreatic cancer with specific genetic changes. One study demonstrated that this combination controlled the disease for at least 12 weeks in several patients, suggesting it might help stabilize the cancer temporarily. In this trial, participants will receive both niraparib, which stops enzymes that tumors need to grow, and dostarlimab, which helps the immune system fight cancer cells. Previous studies have reported side effects similar to those of other treatments, but the potential benefits are promising for this difficult-to-treat cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Robert R. McWilliams, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic cancer that has specific genetic mutations (BRCA1/2 or PALB2). Participants should have had no more than two prior chemotherapy treatments, including a platinum agent, and must be in fairly good health with an ECOG performance status of 0 or 1. Pregnant individuals, those who've had certain immune conditions or severe reactions to immunotherapy, and anyone unwilling to use contraception are excluded.

Inclusion Criteria

My diagnosis of pancreatic cancer was confirmed through tissue or cell testing.

Provide written informed consent

Negative pregnancy test done =< 7 days prior to registration for persons of childbearing potential

Exclusion Criteria

I do not have stomach or intestine problems affecting medicine absorption.

I am still recovering from side effects or complications of my last surgery or treatment.

Known hypersensitivity to any component of study treatments

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 on days 1-21 and dostarlimab intravenously on day 1 every 3 weeks for cycles 1-4 and every 6 weeks for subsequent cycles. Cycles repeat every 21 days for up to 2 years.

Up to 2 years

Every 3 weeks for cycles 1-4, then every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, every 3 months until progressive disease, and then every 6 months for up to 5 years.

Up to 5 years

30 days post-treatment, then every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Niraparib

Trial Overview The trial is testing the combination of Niraparib, which blocks enzymes needed for tumor growth, and Dostarlimab, an antibody that may help the immune system fight cancer. It's a phase II study designed to see how well these drugs work together in treating patients whose pancreatic cancer has spread.

How Is the Trial Designed?

Group I: Treatment (niraparib, dostarlimab) Experimental Treatment 2 Interventions

Patients receive niraparib PO QD on days 1-21. Patients also receive dostarlimab IV over 30 minutes on day 1 Q3W for cycles 1-4 and Q6W for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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 3 study involving 800 patients with metastatic pancreatic cancer, ganitumab combined with gemcitabine did not improve overall survival (OS) compared to gemcitabine alone, with median OS of 7.2 months for placebo and similar results for both ganitumab doses (7.0 and 7.1 months).

The combination treatment showed manageable safety with no unexpected toxicities, but circulating biomarkers did not indicate any treatment effect on OS or progression-free survival (PFS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Fuchs, CS., Azevedo, S., Okusaka, T., et al.[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]

Nabpaclitaxel plus S-1 (AS) significantly improved median time to progression (7.1 months) and overall survival (10.2 months) compared to gemcitabine plus S-1 (GS), indicating AS may be a more effective first-line treatment for metastatic pancreatic cancer based on a study of 38 patients.

While both treatments had similar rates of hematological adverse events, AS was associated with a higher risk of sensory neuropathy, suggesting that while AS is effective, it requires careful monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety comparison of nabpaclitaxel plus S-1 and gemcitabine plus S-1 as first-line chemotherapy for metastatic pancreatic cancer. Xu, Y., Guo, X., Fan, Y., et al.[2022]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04409002

Niraparib + Dostarlimab + RT in Pancreatic Cancer It is believed that the combination of dostarlimab, niraparib, and radiation therapy may have a greater effect on metastatic pancreatic cancer cells than when ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.727

Phase II study of niraparib and dostarlimab for the ... The primary endpoint was disease control rate (DCR) at 12 weeks (DCR12) using iRECIST criteria. At least 8 pts with DCR12 in the first 19 ...

3. 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 ... Studies have reported the rate of grade 3 to 4 AEs of 11% and 37% in PD-1 inhibitors and PARPi, respectively. The combination of PARPi and ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT354531

A phase II study of niraparib and dostarlimab with radiation ... Results: We enrolled and treated 15 pts (median age 60 years [range 37-77], 53% male) from 08/2020 to 05/2021. Overall, DCR was 0/15 (95% CI: 0-22%), median PFS ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04673448

Niraparib and TSR-042 for the Treatment of BRCA-Mutated ... This phase IB trial evaluates the effect of niraparib and TSR-042 in treating patients with BRCA-mutated breast, pancreas, ovary, fallopian tube, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.564

A phase II study of niraparib and dostarlimab with radiation ... We conducted a phase 2 study of niraparib and dostarlimab with radiation in a biomarker unselected PDAC population given PARP inhibitors' immunomodulatory and ...

7. 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 ...

8. 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.