Niraparib + Dostarlimab for Head and Neck Cancer

Not currently recruiting at 1 trial location

Overseen By UCCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trisha Wise-Draper

Must not be taking: Steroids

Disqualifiers: Nasopharyngeal tumors, Salivary gland tumors, 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: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, dostarlimab (an immunotherapy) and niraparib (a PARP inhibitor), to evaluate their effectiveness in treating head and neck cancer that has recurred or spread. The goal is to determine how well this combination shrinks tumors or stops their growth. Individuals diagnosed with head and neck cancer that is no longer treatable with surgery or radiation, and who can swallow pills, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on steroids, you cannot take more than the equivalent of 10mg of prednisone daily.

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

Research shows that combining niraparib and dostarlimab is generally safe for patients. Past studies found no major safety concerns when using these drugs together in ovarian cancer patients. Dostarlimab alone has also been used safely in other treatments.

The advanced stage of this trial suggests confidence in the treatment's safety. While all medications can have side effects, existing research offers reassurance about the safety of using niraparib and dostarlimab together. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Niraparib and Dostarlimab for head and neck cancer because it offers a novel approach compared to traditional treatments like chemotherapy and radiation. Niraparib is a PARP inhibitor, which works by targeting cancer cells' ability to repair their DNA, potentially enhancing the effectiveness of cancer treatment. Dostarlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, they form a powerful duo that not only targets cancer cells directly but also boosts the immune response against them, offering hope for improved outcomes in patients.

What evidence suggests that the combination of niraparib and dostarlimab could be effective for head and neck cancer?

This trial investigates the effectiveness of combining two drugs, niraparib and dostarlimab, for treating head and neck squamous cell carcinoma (HNSCC) that has recurred or metastasized. These drugs have shown promise in treating other cancers, such as ovarian cancer. Niraparib prevents cancer cells from repairing themselves, while dostarlimab enhances the immune system's ability to attack cancer cells. Early results suggest this combination might improve treatment response in patients with HNSCC. However, further research is necessary to confirm its effectiveness for this specific cancer type. ^{2 3 6 7 8}

Who Is on the Research Team?

Trisha Wise-Draper, MD,PhD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or metastatic non-cutaneous head and neck cancers (HNSCC) that can't be cured by surgery or radiation. Participants must be able to swallow pills, have a reasonable level of physical function (ECOG ≤2), and not have had severe side effects from previous cancer treatments, except hair loss. Those who've had both immunotherapy and PARP inhibitors, certain allergies, nasopharyngeal/salivary gland tumors, uncontrolled illnesses, or need high-dose steroids can't join.

Inclusion Criteria

My head or neck cancer has returned or spread and cannot be removed by surgery or cured with radiation.

I can take care of myself but might not be able to do heavy physical work.

You need to be able to swallow pills.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

My cancer is in the nasopharynx or salivary glands.

I have been treated with both immunotherapy and PARP inhibitors before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of niraparib and dostarlimab. Niraparib is administered daily, and dostarlimab is given via IV infusion every 21 days for the first 4 doses, then every 6 weeks.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and progression-free survival.

30 days

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Niraparib

Trial Overview The study tests the effectiveness of combining two drugs: Niraparib (a pill) and Dostarlimab (an injection), in patients with advanced HNSCC. The goal is to see how well this combination works in shrinking or controlling the cancer.

How Is the Trial Designed?

Group I: Niraparib & Dostarlimab Experimental Treatment 2 Interventions

Niraparib starting on Day 0. Niraparib will be administered as continuous daily dose, orally 200 or 300 mg. Dostarlimab IV administered via a 30-minute infusion on Day 1 of every 21 day cycle. 500mg for first 4 doses followed by 1000 mg every 6 weeks.

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?

Trisha Wise-Draper

Lead Sponsor

Trials

6

Recruited

230+

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

The study investigates the safety and effectiveness of combining niraparib, a PARP inhibitor, with dostarlimab, an immune checkpoint inhibitor, in treating advanced non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) in patients with homologous recombination deficiency (HRD) and PD-L1 expression of 1% or higher.

A total of 700 to 1000 patients will be screened to find 70 eligible participants, with the primary goal of assessing progression-free survival, while also evaluating overall survival and safety, highlighting the potential for this combination therapy to enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Phase II Single-arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non-small-cell Lung Cancer and/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design. Passiglia, F., Bironzo, P., Righi, L., et al.[2021]

In a phase 2 study involving 158 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of buparlisib (a pan-PI3K inhibitor) and paclitaxel significantly improved median progression-free survival to 4.6 months compared to 3.5 months with placebo plus paclitaxel, indicating enhanced clinical efficacy.

While the buparlisib group experienced a higher rate of grade 3-4 adverse events (82%) compared to the placebo group (72%), the safety profile was considered manageable, suggesting that buparlisib could be a viable second-line treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Soulières, D., Faivre, S., Mesía, R., et al.[2022]

In a phase II trial involving 41 patients with operable head and neck squamous cell carcinoma (HNSCC), preoperative treatment with olaparib, either alone or in combination with cisplatin or durvalumab, was found to be safe and resulted in a significant reduction in tumor cell proliferation, as indicated by a decrease in Ki67 of at least 25% in 44.8% of treated patients.

The treatment also modulated the tumor microenvironment, leading to increased levels of PD-L1 and changes in macrophage polarization, suggesting that combining olaparib with other therapies may enhance its antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. Moutafi, M., Koliou, GA., Papaxoinis, G., et al.[2023]

In a pilot study involving 12 patients with recurrent and metastatic head and neck squamous cell carcinoma, the maximum tolerated dose of the PI3K inhibitor buparlisib was determined to be 100 mg daily when combined with cetuximab, and this combination was well-tolerated with no dose-limiting toxicities observed.

The combination treatment showed promising results, with one patient achieving a partial response and four others maintaining stable disease, indicating potential benefits for patients who had previously been treated with cetuximab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent or metastatic head and neck cancer. Brisson, RJ., Kochanny, S., Arshad, S., et al.[2022]

Niraparib, a DNA damage repair inhibitor, significantly increased the sensitivity of four head and neck cancer cell lines to both photon and proton radiotherapy, suggesting it could enhance treatment effectiveness.

The study found that niraparib not only reduced colony formation in some cell lines but also increased the relative biological effectiveness (RBE) of protons compared to photons, indicating a potential advantage of proton therapy when combined with niraparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells. Wang, L., Cao, J., Wang, X., et al.[2021]

Citations

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

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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04313504

NCT04313504 | Study Evaluating the Efficacy of Niraparib ... The purpose of this study is to determine the best overall response of the combination of dostarlimab and niraparib in patients with recurrent and/or metastatic ...

3. 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.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6046

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

5. onclive.com onclive.com/view/data-for-first-line-dostarlimab-and-niraparib-in-advanced-ovarian-cancer-the-first-trial

Data for First-Line Dostarlimab and Niraparib in Advanced ... Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for dostarlimab plus niraparib in advanced ovarian cancer.

6. 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.

7. 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.

8. 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 ...