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

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests two drugs, niraparib and dostarlimab, to evaluate their combined effectiveness against small cell lung cancer and high-grade neuroendocrine carcinomas. Niraparib prevents cancer cells from repairing damaged DNA, potentially leading to cell death, while dostarlimab, an immunotherapy drug, aids the immune system in attacking the cancer. This trial may suit individuals with small cell lung cancer or certain neuroendocrine cancers who have previously tried at least one other treatment. 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 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.

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

Research shows that the combination of niraparib and dostarlimab is generally well-tolerated by patients. Previous studies have found that these treatments can help slow the growth or spread of cancers, such as ovarian cancer.

Patients commonly report side effects like tiredness, nausea, and low blood cell counts. However, these side effects are usually manageable, and doctors closely monitor them during treatment.

Since researchers have studied niraparib and dostarlimab in different types of cancer, there is substantial evidence that they are relatively safe when used together. It is important to remember that everyone reacts differently, and healthcare providers will ensure patient safety and address any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combination of niraparib and dostarlimab for small cell lung cancer because it offers a new approach to tackling this aggressive disease. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, dostarlimab is an immunotherapy that helps the body's immune system recognize and fight cancer cells. Niraparib, a PARP inhibitor, works by preventing cancer cells from repairing their DNA, leading to their death. This dual-action strategy could potentially improve outcomes by both enhancing immune response and directly targeting cancer cell survival mechanisms.

What evidence suggests that niraparib and dostarlimab could be effective for small cell lung cancer?

Research shows that using niraparib and dostarlimab together might help treat small cell lung cancer. In this trial, participants will receive both niraparib and dostarlimab. Niraparib blocks a protein that repairs damaged DNA in cells. When cancer cells can't repair their DNA, they may die. Dostarlimab helps the immune system attack cancer cells, potentially stopping their growth and spread. Previous studies with similar treatments have shown positive results in other types of cancer, suggesting these drugs could work well together. While data collection for small cell lung cancer continues, the science behind these drugs supports their potential effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Carl Gay, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04701307

Niraparib and Dostarlimab for the Treatment of Small Cell ...

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

2.

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.

3.

gsk.com

gsk.com/en-gb/media/press-releases/gsk-highlights-new-data-in-non-small-cell-lung-cancer-and-endometrial-cancer-at-esmo/

GSK highlights new data in non-small cell lung cancer and ...

Late-breaking data from head-to-head PERLA trial shows favourable numerical trend in overall survival (OS) results.

4.

withpower.com

withpower.com/trial/phase-3-carcinoma-small-cell-1-2021-1b1a1

Niraparib + Dostarlimab for Small Cell Lung Cancer

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

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.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12146980/

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.

clinical-lung-cancer.com

clinical-lung-cancer.com/article/S1525-7304(22)00115-2/fulltext

Results from Cohort E of the Phase I GARNET Trial

Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non–small cell lung cancer (NSCLC ...

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 ...