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

NCT04701307 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-0412NCI-2020-13698
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Lung Small Cell Carcinoma; Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (2)

• 6-month Progression free survival (PFS)

  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)

  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 Outcomes (4)

• 12-week disease control rate

  At 12 weeks

• Progression free survival

  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)

  From the start of study treatment to the date of death by any cause, assessed up to 5 years

• Incidence of adverse events (AEs)

  Up to 90 days post-treatment

Study Arms (1)

Treatment (niraparib, dostarlimab)

EXPERIMENTAL

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.

Biological: Dostarlimab; Drug: Niraparib

Interventions

Dostarlimab BIOLOGICAL

Given IV

Also known as: 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, TSR-042, TSR042

Treatment (niraparib, dostarlimab)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Treatment (niraparib, dostarlimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MDAndersonCancerCenterWebsite

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine; Lung Neoplasms

Interventions

dostarlimab; Immunoglobulin G; Disulfides; niraparib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Carl M Gay, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 8, 2021
• Study Start: February 1, 2021
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)