Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer

NCT04673448 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1005140NCI-2020-1163610020
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase IB trial evaluates the effect of niraparib and TSR-042 in treating patients with BRCA-mutated breast, pancreas, ovary, fallopian tube, or primary peritoneal cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). 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 TSR-042, 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 TSR-042 may kill more cancer cells.

Conditions

Anatomic Stage III Breast Cancer AJCC v8; BRCA-Associated Malignant Neoplasm; BRCA Hereditary Ovarian Carcinoma; Metastatic BRCA Hereditary Breast Carcinoma; Metastatic Breast Carcinoma; Metastatic Fallopian Tube Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Ovarian Carcinoma; Metastatic Pancreatic Carcinoma; Metastatic Primary Peritoneal Carcinoma; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Stage III Fallopian Tube Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage III Primary Peritoneal Cancer AJCC v8; Stage IV Fallopian Tube Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IV Primary Peritoneal Cancer AJCC v8; Unresectable Breast Carcinoma; Unresectable Fallopian Tube Carcinoma; Unresectable Malignant Solid Neoplasm; Unresectable Ovarian Carcinoma; Unresectable Pancreatic Carcinoma; Unresectable Primary Peritoneal Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Best objective response

  Will be defined as a complete response (CR) or partial response (PR), confirmed and unconfirmed, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 using investigator's review.

  5 years

Secondary Outcomes (5)

• Incidence of adverse events

  5 years

• Progression-free survival (PFS)

  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 5 years

• Duration of response (DOR)

  Time from the initial response (CR or PR) until the time of first documentation of disease progression, assessed up to 5 years

• Disease control (DC)

  5 years

• Overall survival

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

Study Arms (1)

Treatment (niraparib, dostarlimab)

EXPERIMENTAL

Patients receive niraparib PO QD on days 1-28 of cycle 1. Beginning cycle 2, patients receive niraparib PO QD on days 1-21 and dostarlimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 6, patients receive niraparib PO QD on days 1-42 and dostarlimab IV over 30 minutes on day 1. Cycles repeat every 42 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy, blood sample collection, and CT or MRI throughout the study.

Biological: Dostarlimab; Drug: Niraparib; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Treatment (niraparib, dostarlimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Treatment (niraparib, dostarlimab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, CT Scan

Treatment (niraparib, dostarlimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI, MRI Scan

Treatment (niraparib, dostarlimab)

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, Dostarlimab-gxly, Jemperli

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 breast, pancreas, ovary, fallopian tube or primary peritoneal cancer that is unresectable or metastatic, with a pathogenic mutation in BRCA1 or BRCA2 (either germline or somatic) as confirmed by next generation gene sequencing such as University of Washington (UW) OncoPlex assay or equivalent, and who have experienced progression or been intolerant to standard therapies for their disease.
• Breast cancer patients with or without HER2+, estrogen receptor (ER)+, and/or progesterone receptor (PR)+ disease, as determined by pathological report, are allowed
• Participant must be able and willing to undergo pre-treatment and on-treatment biopsy
• Participant must have life expectancy of 4 months or greater
• Tumor must be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Participant must be \>= 18 years of age
• Patient must be able to tolerate oral medication
• 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

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have had major surgery =\< 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
• Prior treatment with both PARP inhibitor and immune checkpoint inhibitor blockade either sequentially or together including inhibitors of PD1, PD-L1 or CTLA4 is not allowed. Patients may have had either PARP inhibitor or Immune checkpoint inhibitor previously but not within 3 weeks of starting treatment for prior PARP inhibitor or 12 weeks or 5x the half-life (whichever is shorter) for prior immune checkpoint inhibitors
• Participant must not have received investigational therapy =\< 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
• Participant must not have 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 (TSR-042) 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 in situ cervical cancer that has been definitively treated or a BRCA-related cancer (i.e., breast, prostate, pancreas or ovarian)
• Participant must not have a known partial or complete bowel obstruction that is incompatible with oral feeding and/or absorption of oral medications
• Patient experienced \>= grade 3 immune-related adverse event (AE) with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
• Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy

Sponsors & Collaborators

• University of Washington: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Fallopian Tube Neoplasms; Neoplasm Metastasis; Ovarian Neoplasms; Pancreatic Neoplasms

Interventions

dostarlimab; Immunoglobulin G; Disulfides; niraparib; Biopsy; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

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; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Elizabeth M. Swisher

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 17, 2020
• Study Start: October 18, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)