Niraparib + Dostarlimab for Head and Neck Cancer

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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, dostarlimab and niraparib, in patients with head and neck cancer that has come back or spread. Dostarlimab helps the immune system attack cancer, while niraparib prevents cancer cells from repairing themselves. Niraparib is an oral drug approved for maintenance treatment in ovarian, fallopian tube, or primary peritoneal cancer.

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.

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

Research shows that Niraparib, a drug that helps repair damaged DNA, has potential when combined with radiotherapy for head and neck cancer. While there is no direct evidence for the combination of Niraparib and Dostarlimab, similar drugs have shown promise in improving survival rates in head and neck cancer. ^{1 2 3 4 5}

How is the drug combination of Niraparib and Dostarlimab unique for head and neck cancer?

The combination of Niraparib and Dostarlimab is unique because it targets DNA repair deficiencies in cancer cells, potentially enhancing the immune response against tumors. This approach is different from standard treatments as it combines a PARP inhibitor (Niraparib) with an immune checkpoint inhibitor (Dostarlimab), which may work together to improve treatment effectiveness. ^{1 5 6 7 8}

Research Team

Trisha Wise-Draper, MD,PhD

Principal Investigator

University of Cincinnati

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Osimertinib and dihydroartemisinin: a novel drug combination targeting head and neck squamous cell carcinoma. [2022]

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

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. [2023]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis. [2022]

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

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells. [2021]

6. United States 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. [2021]

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

Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints. [2022]

8. England 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. [2022]