Radiation, Immunotherapy and PARP Inhibitor in Triple Negative Breast Cancer

NCT04837209 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-649
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is looking to see whether the combination of Dostarlimab and Niraparib plus Radiation Therapy (RT) is safe and effective in participants with metastatic triple negative breast cancer. The names of the study treatment involved in this study are:

• Dostarlimab
• Niraparib
• Radiation Therapy (RT), which is given per standard of care.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Keywords

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)-RECIST

  Primary endpoint of the study is ORR as measured by RECIST v1.1. ORR will be estimated with the 95% confidence interval, based on the exact binomial distribution

  Enrollment to end of treatment up to 5 years

Secondary Outcomes (4)

• Overall response rate (ORR) by irRECIST criteria

  Enrollment to end of treatment up to 5 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  Enrollment to end of treatment up to 5 years

• Overall survival (OS)

  First day of study treatment to the date of death due to any cause, assessed up to 5 years

• Progression-free survival (PFS)

  First day of study treatment to the date of disease progression or death due to any cause, whichever came first, assessed up to 5 years

Other Outcomes (2)

• Changes in TILs

  Enrollment to end of treatment up to 5 years

• ctDNA

  Enrollment to end of treatment up to 2 years

Study Arms (1)

Niraparib + Dostarlimab + Radiation therapy

EXPERIMENTAL

Study cycle length is 3 weeks. Participants will receive: * Niraparib 1x daily during each study cycle * Dostarlimab 1x every 3 weeks for 4 study cycles, then 1x every 6 weeks beginning on Cycle 5 * Radiation therapy will be given on Days 1, 2, and 3 of Cycle 1.

Drug: Niraparib; Drug: Dostarlimab; Radiation: Radiation therapy

Interventions

Niraparib DRUG

Capsule, taken by mouth

Also known as: Zejula

Niraparib + Dostarlimab + Radiation therapy

Dostarlimab DRUG

Intravenous infusion

Also known as: TSR-042, WBP-285

Niraparib + Dostarlimab + Radiation therapy

Radiation therapy RADIATION

Radio Therapy

Niraparib + Dostarlimab + Radiation therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• ECOG performance status ≤ 1
• Histologically or cytologically-confirmed TNBC (ER \<1%, PR \<1%, HER-2-neu 0-1+ by IHC or non-FISH-amplified63. ER-low, PR-low (defined as ER and/or PR 1-10%) and HER2-negative patients may also be eligible, as per treating MD discretion).
• Metastatic or recurrent TNBC.
• Prior progression on immune-checkpoint inhibitor and/or PDL1-negative. Note: PDL1-status may be determined on tissues from either primary or mTNBC. PD-L1 status must be determined by an FDA-approved assay approved for breast cancer, such as PharmDx IHC (22C3) for pembrolizumab, Ventana (SP142) for atezolizumab
• No more than 2 prior lines of systemic therapy for inoperable/recurrent or metastatic disease.
• Note: Prior line of systemic therapy includes targeted or biologic agents in combination or the absence of chemotherapy
• Radiation is clinically indicated for local control or palliation.
• At least one tumor for which RT is considered clinically appropriate.
• At least one radiographically-confirmed metastases index lesion that will not undergo RT and is measurable based on RECIST v1.1.
• Prior therapy with targeted agents or other forms of immunotherapy is allowed
• Prior RT is permitted, provided the treating radiation oncologist deems that study RT treatment planning guidelines can be achieved.
• Available archived tumor tissue of a metastatic tumor collected up to 28 days prior to registration. If archival tissue is unavailable, participant willingness to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 28 days prior to study registration.
• Adequate organ function (assessed within 8 days prior to initiation of protocol treatment, unless otherwise indicated) as follows:
• Hematology

You may not qualify if:

• Participants who meet any of the following criteria will be excluded:
• Known germline or somatic BRCA mutation-positive status
• Known active brain metastases or LMD (leptomeningeal disease). Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging \[using the identical imaging modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment.
• Known additional malignancy that progressed or required treatment in the last 2 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Prior treatment with either a PARP inhibitor or ICI is permitted, however, prior receipt of both therapies is excluded
• Receipt of \>2 lines of chemo in the metastatic setting (including targeted or biologic agents in combination or the absence of chemotherapy)
• Hypersensitivity to niraparib or dostarlimab components or its excipients.
• Participation in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks (or at least 5 half-lives from previous therapy) of the first dose of study treatment.
• Receipt of prior cytotoxic therapy or targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., \> Grade 1 or at baseline) from adverse events due to a previously administered agent, including grade 2 alopecia.
• Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Patients who have undergone any major surgery within 3 weeks prior to study entry: patients must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• 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.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Use of local corticosteroid injections (e.g. intra-articular injections), inhaled, intranasal, ophthalmic, and topical corticosteroids, and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan pre-medication) are allowed.
• Known history of/active, non-infectious pneumonitis requiring treatment with steroids or has history of/active interstitial lung disease.
• Active infection requiring systemic therapy.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Sibley Memorial Hospital: collaborator
• Duke University: collaborator
• University of Pennsylvania: collaborator

Study Sites (4)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

niraparib; dostarlimab; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Steven J Isakoff, MD

  Massachusetts General Hospital

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: April 8, 2021
• Study Start: July 21, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (4)