Niraparib + Dostarlimab for Small Cell Lung Cancer

Overseen By Carl M Gay, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: PARP inhibitors, Immunotherapy

Disqualifiers: MDS, AML, Uncontrolled infection, 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: Up to 5 years

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of niraparib and dostarlimab in treating small cell lung cancer and other high-grade neuroendocrine carcinomas. 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 dostarlimab, 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 dostarlimab may help to control the diseases.

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, if you are on corticosteroids, you can continue as long as the dose is equivalent to 10 mg of prednisone or less and stable for at least 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Niraparib and Dostarlimab for Small Cell Lung Cancer?

Dostarlimab has shown effectiveness in treating certain types of cancer, like endometrial cancer, by helping the immune system attack cancer cells. Niraparib has been studied as a maintenance treatment for small cell lung cancer, showing potential benefits in patients who responded to initial chemotherapy. ^{1 2 3 4 5}

What makes the drug combination of Niraparib and Dostarlimab unique for treating small cell lung cancer?

The combination of Niraparib and Dostarlimab is unique because it targets cancer cells with DNA repair deficiencies, using Niraparib to increase DNA damage and Dostarlimab to enhance the immune response, potentially offering a new approach for small cell lung cancer that lacks standard treatments. ^{1 2 5 6 7}

Research Team

Carl Gay, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with small cell lung cancer or high-grade neuroendocrine carcinomas who've had at least one prior treatment can join. They must be generally healthy, not pregnant, and agree to contraception. Excluded are those with certain infections, recent major surgery, known allergies to trial drugs, brain metastases, autoimmune diseases requiring recent treatment, a second cancer within the last two years, or severe blood disorders from past treatments.

Inclusion Criteria

I am over 45 and have not had a period for more than a year.

I am not pregnant and agree to use birth control during and after the study, or I cannot become pregnant.

Your blood clotting tests need to be within a certain range, unless you are already taking medication to prevent blood clots.

Exclusion Criteria

I don't have active brain cancer symptoms and any previous brain cancer has been treated and is stable.

I have never been diagnosed with MDS or AML.

I have never been treated with both PARP inhibitors and immunotherapy at the same time.

Timeline

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 of cycles 1-4, and on days 1-42 of subsequent cycles. Dostarlimab is administered intravenously on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-4 and every 42 days for subsequent cycles.

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs within 90 days post-treatment, every 6 months for 2 years, then annually for 3 years.

5 years

Treatment Details

Interventions

• Dostarlimab
• Niraparib

Trial Overview The trial is testing niraparib (a PARP inhibitor that blocks cancer cells' DNA repair) combined with dostarlimab (an immunotherapy antibody). It's for patients whose disease didn't respond well to initial treatments. The study aims to see if this combination helps control the disease better than existing therapies.

Participant Groups

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

Patients receive niraparib PO QD on days 1-21 of cycles 1-4, and on days 1-42 of subsequent cycles. Patients also receive dostarlimab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycles 1-4 and every 42 days for subsequent cycles 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., 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]

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]

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]

References

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

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. [2023]

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

Dostarlimab: First Approval. [2021]

3. China pubmed.ncbi.nlm.nih.gov

A single-arm, prospective study of apatinib mesylate plus pemetrexed in patients of advanced non-squamous non-small cell lung cancer after failure of previous chemotherapy. [2022]

4. China pubmed.ncbi.nlm.nih.gov

Breakthroughs in the treatment of advanced squamous-cell NSCLC: not the neglected sibling anymore? [2020]

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

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study. [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. United States pubmed.ncbi.nlm.nih.gov

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