Niraparib and Dostarlimab for the Treatment of Small Cell Lung Cancer and Other High-Grade Neuroendocrine Carcinomas

April 21, 2026 updated by: M.D. Anderson Cancer Center

Niraparib (PARP Inhibitor) Plus Dostarlimab (Anti-PD1) for Small Cell Lung Cancer (SCLC) and Other High-Grade Neuroendocrine Carcinomas (NEC)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine objective response rate (ORR) and 6-month progression free survival (PFS) in response to combined niraparib plus dostarlimab in patients with recurrent small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas (NECs).

SECONDARY OBJECTIVES:

I. To evaluate toxicity of combined niraparib plus dostarlimab (PARP inhibition plus anti-PD-1) in patients with recurrent SCLC and other high-grade NECs.

II. To determine overall survival (OS), PFS, disease control rate (response plus stable disease > 12 weeks) to combined niraparib plus dostarlimab in patients with recurrent SCLC and other high-grade NECs.

EXPLORATORY OBJECTIVE:

I. To determine treatment-related changes in immune profiles or other biomarker in response to combined niraparib plus dostarlimab in patients with recurrent SCLC and other high-grade NECs.

OUTLINE:

Patients receive niraparib orally (PO) once daily (QD) on days 1-21 of cycles 1-4, and on days 1-42 of subsequent cycles. Patients also receive dostarlimab intravenously (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.

After completion of study treatment, patients are followed up within 90 days, every 6 months for 2 years, then annually for 3 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant must have unresected or locally advanced small cell lung cancer (Cohort 1) or high-grade neuroendocrine carcinoma (Cohort 2) confirmed by staff pathologist. High-grade neuroendocrine carcinoma of prostate (e.g. aggressive variant prostate cancer, small cell of prostate, etc.) are excluded
  • Patients must have had at least one prior line of systemic therapy directed at their malignancy
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Participant must be >= 18 years of age
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min using the Cockcroft-Gault equation
  • Total bilirubin =< 1.5 x ULN (=< 2.0 in patients with known Gilberts syndrome) OR direct bilirubin =< 1 x ULN
  • Aspartate aminotransferase and alanine aminotransferase =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Participant receiving corticosteroids may continue as long as their dose equivalent to 10 mg prednisone or less and is stable for least 4 weeks prior to initiating protocol therapy
  • Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment

  • Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees use an adequate method of contraception from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):

    • >= 45 years of age and has not had menses for > 1 year
    • Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
    • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
    • Pelvic irradiation
  • Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment
  • Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
  • Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

  • Participant must not be simultaneously enrolled in any interventional clinical trial
  • Participant must not have previously received a simultaneous combination of PARP inhibitor and immune checkpoint blockade (immunotherapy)
  • Participant must not have had major surgery =< 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
  • Participant must not have received investigational therapy =< 4 weeks prior initiating protocol therapy
  • Participant has had radiation therapy encompassing > 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to day 1 of protocol therapy
  • Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients
  • Participant must not have received a transfusion (platelets or red blood cells) =< 4 weeks prior to initiating protocol therapy
  • Participant must not have received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
  • Participant has had any known grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment
  • Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  • Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
  • Participant must not have had diagnosis, detection, or treatment of another type of cancer =< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
  • Participant must not have known, symptomatic brain or leptomeningeal metastases. Patients should have magnetic resonance imaging (MRI) brain with and without contrast (or computed tomography [CT] head with and without contrast) within 4 weeks prior to initiation of therapy. If history of known brain metastases, these must be treated with completion of treatment at least two weeks prior to initiation of therapy. Known brain metastases must be clinically stable and asymptomatic
  • Patient experienced >= grade 3 immune-related adverse event (AE) with prior immunotherapy
  • Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy in excess of 10 mg prednisone (or equivalent) or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
  • Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected)
  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Participant must not have a history of interstitial lung disease
  • Participant has received a live vaccine within 14 days of initiating protocol therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (niraparib, dostarlimab)
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.
Drug: Niraparib
Given PO
Other Names:
  • MK-4827
  • MK4827
Biological: Dostarlimab
Given IV
Other Names:
  • TSR-042
  • TSR042
  • ANB011
  • Immunoglobulin G4, Anti-programmed Cell Death Protein 1 (PDCD1) (Humanized Clone ABT1 Gamma4-chain), Disulfide with Humanized Clone ABT1 Kappa-chain, Dimer
  • TSR 042

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
6-month Progression free survival (PFS)
Time Frame: Time from the start of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed at 6 months
Defined as the number (or fraction) of patients who are alive without evidence of progression at 6 months from initiation of therapy. Progression will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.)1.1 criteria using investigator's review. As there is no comparator arm, the rates will be considered in the context of historical controls. Will be performed using Kaplan-Meier methods for each cohort. Quartiles (i.e. 25th percentile, median, 75th percentile) and associated two-sided 95% confidence intervals will be provided. Estimates of PFS at 6-months will be estimated from Kaplan-Meier survival curve.
Time from the start of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed at 6 months
Objective response rate (ORR)
Time Frame: At 3 months
Defined as the percentage of patients with complete response (CR) or partial response (PR), as assessed by RECIST v.1.1 criteria using independent central review by MD Anderson Quantitative Imaging Analysis Core. As there is no comparator arm, the rates will be considered in the context of historical controls.
At 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
12-week disease control rate
Time Frame: At 12 weeks
Defined as the percentage of patients with CR, PR, or stable disease, as assessed by RECIST v.1.1 criteria using (independent central or investigator's) review at 12 weeks from initiation of therapy.
At 12 weeks
Progression free survival
Time Frame: Time from the start of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 12 months
Progression will be assessed by RECIST v.1.1 criteria using investigator's review. Will be performed using Kaplan-Meier methods for each cohort. Quartiles (i.e. 25th percentile, median, 75th percentile) and associated two-sided 95% confidence intervals will be provided. Estimates of PFS at 6-months and 12-months will be estimated from Kaplan-Meier survival curve.
Time from the start of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 12 months
Overall survival (OS)
Time Frame: From the start of study treatment to the date of death by any cause, assessed up to 5 years
Will be performed using Kaplan-Meier methods for each cohort. Quartiles (i.e. 25th percentile, median, 75th percentile) and associated two-sided 95% confidence intervals will be provided. Estimates of OS at 6-months and 12-months will be estimated from Kaplan-Meier survival curve.
From the start of study treatment to the date of death by any cause, assessed up to 5 years
Incidence of adverse events (AEs)
Time Frame: Up to 90 days post-treatment
Defined as frequency and grade of adverse events. All AEs will be assessed by the investigator for severity according to Common Terminology Criteria for Adverse Events v5.0.
Up to 90 days post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carl M Gay, MD,PHD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 6, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-0412 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2020-13698 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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