Stage I Breast CancerPhase 2NCT04584255
Niraparib + Dostarlimab In BRCA Mutated Breast Cancer
A Phase 2 study testing Niraparib and Dostarlimab in people with Stage I Breast Cancer and Stage II Breast Cancer, run by Dana-Farber Cancer Institute at 8 sites in United States.
Trial summary
This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations. The names of the study drugs involved in this study are: Niraparib (Zejula) Dostarlimab Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer
- What is being tested?
- Niraparib and Dostarlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 8 sitesUnited States
- Study dates
- 21 Jan 2021to 17 Jul 2029
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet the following criteria on screening examination to be eligible to participate in the study. Laboratory assessments for eligibility must be completed within 14 days prior to the date of registration. Diagnostic imaging, such as MRIs and CT scans, must be performed within 28 days of the planned treatment start.
- Participants must have histologically or cytologically confirmed invasive breast cancer Stage I to III with primary tumor size at least 1.0 cm defined by physical exam or imaging (whichever is larger). In the case of a multifocal, multicentric, or bilateral disease, the largest lesion must be ≥ 1.0 cm and designated as the "index" lesion for tumor evaluations. Patients with inflammatory breast carcinoma are not eligible.
- Participants must have documentation of estrogen receptor (ER) and progesterone receptor (PR) testing by IHC according to local institutional guidelines in a CLIA-approved setting. Central confirmation of ER/PR status is not required. All tumors must be HER2 negative.
- Arms A and B: Target lesion must be ER and PR negative (<10% staining) by local review.
- Arm C: Target lesion must be ER and/or PR positive (>10% staining) by local review.
- Participants must have documented HER2-negative invasive tumor according to local institutional guidelines in a CLIA-approved setting. Central confirmation of HER2 status is not required. HER2 negative is defined as:
Show all 34Show fewer
- 0 or 1+ by IHC, OR
- Lack of gene amplification with HER2/CEP17 ratio < 2 by ISH, OR
- Copy number < 6 by ISH
- Participants must have documented germline mutation in BRCA1, BRCA2 or PALB2 that is deleterious or suspected to be deleterious (known or predicted to be detrimental/lead to loss of function). Mutation must be identified through a CLIA-approved laboratory. Final determination of eligibility for any discordant results in pathogenicity will be made by the sponsor-investigator. A formal eligibility exception will not be required in these cases as long as approval by overall study PI is granted and documented.
- Participants with multifocal, multicentric or bilateral disease are eligible if at least one lesion meets criteria for the study. In this circumstance, the investigator must determine which will represent the target lesion to be assessed for response. This should remain consistent throughout the study. The target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements.
- Participants with an eligible target lesion, and another small HER2+ tumor (for example, < 6 mm), may be eligible for enrollment following discussion and agreement with the overall principal investigator. A formal eligibility exception will not be required in these cases as long as approval by the sponsor-investigator is granted and documented.
- Female or male ≥ 18 years of age
- Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla by physical examination or imaging, axillary tissue acquisition is not required. For patients with a clinically negative axilla by examination and imaging, tissue acquisition is not required. For equivocal imaging findings, tissue acquisition (a needle aspiration, core biopsy) is required. Sentinel Lymph Node (SLN) biopsy before neoadjuvant therapy is not allowed.
- ECOG performance status of 0 or 1
- Adequate organ and bone marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dl
- Total serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (≤2.0 in patients with documented Gilbert's Syndrome)
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN
- Serum or plasma creatinine ≤ 1.5 × institutional ULN, OR calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault equation
- International normalized ratio (INR) OR prothrombin time (PT) ≤1.5× ULN. Participants who are receiving anticoagulant therapy are eligible as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) must be ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Premenopausal women must have a negative urine or serum pregnancy test within 7 days of treatment start. Women are considered non-childbearing (by other than medical reasons) if they:
- are ≥45 years of age and without menses for >1 year
- have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy with a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- are 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. See list of acceptable birth control methods. 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.
- Male and female participants of childbearing potential must agree to adhere to adequate contraception as defined in the protocol for the duration of study participation and for 150 days after the last dose of study treatment.
- Female participants must agree to not breastfeed during the study or for 150 days after the last dose of study treatment.
- Participants must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
- Ability to understand and willingness to sign an informed consent document.
- Ability to swallow and retain oral medication.
- Patients undergoing breast conserving therapy (ie lumpectomy) should not have any contraindications to radiation therapy.
- Participants must be willing to undergo the mandatory research biopsy at baseline and after 3 weeks on study treatment. Participants who undergo an attempted research biopsy procedure for the purpose of this protocol and in whom inadequate tissue is obtained are not required to undergo a repeat biopsy in order to continue on the protocol.
Who cannot join
- Stage IV breast cancer.
- Concurrent therapy with any other investigational product
- Prior treatment for the current breast cancer, including prior chemotherapy, immune therapy, hormonal therapy, radiation, or investigational therapy for this diagnosis.
- Excisional biopsy of the primary tumor and/or excision of axillary lymph nodes, including SLNB, prior to study treatment.
- Participants with a history of malignancy are ineligible except in the following circumstances:
- Individuals with a history of invasive breast cancer are not eligible unless they have been disease-free for a minimum of three years.
Show all 23Show fewer
- Individuals with a malignancy history other than invasive breast cancer are eligible if they have no active malignancy and are deemed by the investigator to be at low risk for recurrence of that malignancy.
- Individuals with the following cancer history are eligible: adequately treated nonmelanoma skin cancers, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma.
- Other exceptions may exist following agreement with the sponsor-investigator
- Patients with a diagnosis of immunodeficiency, or currently receiving systemic steroid therapy or any other form of immunosuppressive within 7 days prior to the first dose of study treatment. Use of local corticosteroid injections (e.g. intraarticular injections), inhaled, intranasal, ophthalmic, and topical corticosteroids, and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan pre-medication) are allowed.
- Patients with autoimmune disease that has required systemic treatment within 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.
- Patients with a history of interstitial lung disease or pneumonitis.
- Patients who have received a live vaccine within 2 weeks prior to the start of study treatment.
- Patients who have undergone any major surgery within 3 weeks prior to study entry, patients must have recovered to baseline from any effects of any major surgery.
- Patients with concurrent HIV infection are eligible provided they meet the following criteria:
- CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
- No history of AIDS-defining opportunistic infection within 12 months prior to enrollment
- Any medication used in an antiretroviral therapy (ART) regimen must have no known interaction with the study agents
- Patients with active or chronic Hepatitis B or C are eligible provided they meet the liver function laboratory criteria described in 3.1.10 and cannot be on any medication with a known interaction with the study agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric illness/social situations that would limit compliance with study requirements.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to niraparib, dostarlimab, or their excipients.
- Transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
- Known history of myelodysplastic syndrome (MDS) or or acute myeloid leukemia (AML).
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Yale University Cancer Center
New Haven, Connecticut, 06520
Mayo Clinic
Rochester, Minnesota, 55905
University of Washington / Fred Hutchinson Cancer Center
Seattle, Washington, 98109
About this study
Official title: A Phase II Study of Niraparib With Dostarlimab Therapy as Neoadjuvant Treatment for Patients With BRCA-mutated Breast Cancer
This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations.
The names of the study drugs involved in this study are:
- Niraparib (Zejula)
- Dostarlimab
Read the detailed description
The research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies, imaging assessments, and follow up visits.
Participants will receive treatment for 18 weeks. After 18 weeks, participants will be evaluated to determine if a candidate for surgery or if additional treatment outside of the study.
Participants with triple negative breast cancer will be randomized to one of two treatment arms.
- Arm A: Niraparib with Dostarlimab for 18 weeks
- Arm B: Niraparib alone for 3 weeks, followed by Niraparib with Dostarlimab for 15 weeks
Participants with estrogen receptor positive breast cancer will be placed directly into Arm C. There is no randomization for these participants.
- Arm C: Niraparib with dostarlimab for 18 weeks
It is expected that about 62 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that the study drugs, Niraparib and Dostarlimab, are being studied for use in this setting and the research doctors are trying to learn more about the drug combination-the side effects the combination may cause and if it is effective in treating this type of cancer.
The U.S. Food and Drug Administration (FDA) has not yet approved either of the drugs in this study for your type of cancer. Niraparib has been approved by the FDA for treatment of advanced ovarian cancer in BRCA mutation carriers.
The use of Dostarlimab in this research study is experimental, which means that it is not approved by any regulatory auit is not approved by any regulatory authority, including the FDA, for treatment of breast cancer, or any other disease.
- Conditions
- Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, Breast Cancer, HER2-negative Breast Cancer, Germline BRCA1 Gene Mutation
- Being tested
- Niraparib, Dostarlimab
- Keywords
- Invasive Breast Cancer Stage I, Invasive Breast Cancer Stage II, Invasive Breast Cancer Stage III, Breast Cancer, HER2-negative invasive tumor
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Predetermined dosage PO Daily
DostarlimabDrug
Also called TSR042
Predetermined Dosage, IV,q3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A Triple Negative Breast Cancer (TNBC) | Experimental | Participants will be randomized 1:1 to treatment with the combination (Arm A)
* Niraparib-Daily beginning with week 1, day 1
* Dostarlimab-Once every three weeks beginning with week 1, day 1 Receives: Drug: Niraparib; Drug: Dostarlimab |
| Arm B TNBC | Experimental | Participants will be randomized 1:1 to treatment with the combination (Arm B)
* 3-week lead-in of niraparib monotherapy followed by treatment with the combination
* Niraparib Daily beginning with week 1, day 1
* Dostarlimab Once every three weeks beginning with week 4, day 1 Receives: Drug: Niraparib; Drug: Dostarlimab |
| Arm C ER+/HER2- | Experimental | exploratory cohort of estrogen receptor (ER) positive HER2-negative participants will be enrolled to Arm C.
* Niraparib Daily beginning with week 1, day 1
* Dostarlimab Once every three weeks beginning with week 1, day 1 Receives: Drug: Niraparib; Drug: Dostarlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Tumor-infiltrating Lymphocytes (TILs)
Change in TILs score from baseline to cycle 2 day 1; the score is estimated by a pathologist according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines, as the percentage (0-100) of the tumor's stromal area occupied by mononuclear immune cells on a stained tissue slide; higher scores generally correlate with improved survival outcomes and better responses to chemotherapy
Measured: baseline to 21 days (cycle 2 day 1)
Pathologic Complete Response (pCR) Rate in TNBC
The number and percentage of participants achieving pCR without additional neoadjuvant therapy; the residual cancer burden (RCB) method as described by Symmans et al. was used to assess response, with increasing RCB score associated with greater burden of residual disease after surgery; RCB-0 reflects pCR (no residual disease), whereas RCB-I, RCB-II, and RCB-III reflect minimal, moderate, and extensive residual disease, respectively
Measured: 18 weeks
Secondary outcomes (4)
pCR Rate in ER+/HER2- Breast Cancer
The number and percentage of participants achieving pCR without additional neoadjuvant therapy; the residual cancer burden (RCB) method as described by Symmans et al. was used to assess response, with increasing RCB score associated with greater burden of residual disease after surgery; RCB-0 reflects pCR (no residual disease), whereas RCB-I, RCB-II, and RCB-III reflect minimal, moderate, and extensive residual disease, respectively
Measured: 18 weeks
Association Between Change in TILs Score and pCR
The association between change in TILs score (%) from baseline to cycle 2 day 1 (18 weeks) and pCR status (pCR vs. no pCR), evaluated using a two-sample Wilcoxon rank sum test; the odds ratio for a fixed change in TILs estimated using simple logistic regression; TILs score was measured as described in Outcome Measure 1, and because the TILs score reflects a percentage, the change was calculated as the raw difference in TILs score between time points; pCR was measured as described in Outcome Measure 2
Measured: baseline to 18 weeks
Rate of Residual Cancer Burden (RCB)-0/1 Response
The residual cancer burden (RCB) method as described by Symmans et al. was used to assess response, with increasing RCB score associated with greater burden of residual disease after surgery; RCB-0 reflects pCR (no residual disease), whereas RCB-I, RCB-II, and RCB-III reflect minimal, moderate, and extensive residual disease, respectively; an RCB score of 0 or I is considered good response; this Outcome Measure reports the percentage of patients achieving an RCB score of 0 or I vs. not
Measured: 18 Weeks
Treatment-related Adverse Events
Number and percentage of patients with treatment-related, grade 2 or higher adverse events per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: baseline up to 31 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2020
- Study start21 Jan 2021
- Primary completion1 Jul 2025
- Study completion17 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage I Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Johns Hopkins University, GlaxoSmithKline
- Responsible party
- Principal investigator, Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Erica L. Mayer, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04584255
- Sponsor's protocol ID
- 20-371
- Status last verified
- Jun 2026
- First submitted
- 8 Oct 2020
- Last updated
- 24 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Niraparib With Dostarlimab Therapy as Neoadjuvant Treatment for Patients With BRCA-mutated Breast Cancer
- ClinicalTrials.gov ID
- NCT04584255
- Acronym / sponsor ID
- 20-371
- Conditions
- Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, Breast Cancer, HER2-negative Breast Cancer, Germline BRCA1 Gene Mutation
- Keywords
- Invasive Breast Cancer Stage I, Invasive Breast Cancer Stage II, Invasive Breast Cancer Stage III, Breast Cancer, HER2-negative invasive tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Johns Hopkins University, GlaxoSmithKline
- Study start
- 21 Jan 2021 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- 17 Jul 2029 (estimated)
- First posted
- 12 Oct 2020 (actual)
- Results
- Posted 24 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations.
The names of the study drugs involved in this study are:
- Niraparib (Zejula)
- Dostarlimab
Detailed description
The research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies, imaging assessments, and follow up visits.
Participants will receive treatment for 18 weeks. After 18 weeks, participants will be evaluated to determine if a candidate for surgery or if additional treatment outside of the study.
Participants with triple negative breast cancer will be randomized to one of two treatment arms.
- Arm A: Niraparib with Dostarlimab for 18 weeks
- Arm B: Niraparib alone for 3 weeks, followed by Niraparib with Dostarlimab for 15 weeks
Participants with estrogen receptor positive breast cancer will be placed directly into Arm C. There is no randomization for these participants.
- Arm C: Niraparib with dostarlimab for 18 weeks
It is expected that about 62 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that the study drugs, Niraparib and Dostarlimab, are being studied for use in this setting and the research doctors are trying to learn more about the drug combination-the side effects the combination may cause and if it is effective in treating this type of cancer.
The U.S. Food and Drug Administration (FDA) has not yet approved either of the drugs in this study for your type of cancer. Niraparib has been approved by the FDA for treatment of advanced ovarian cancer in BRCA mutation carriers.
The use of Dostarlimab in this research study is experimental, which means that it is not approved by any regulatory auit is not approved by any regulatory authority, including the FDA, for treatment of breast cancer, or any other disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A Triple Negative Breast Cancer (TNBC) | Experimental | Drug: Niraparib, Drug: DostarlimabParticipants will be randomized 1:1 to treatment with the combination (Arm A) * Niraparib-Daily beginning with week 1, day 1 * Dostarlimab-Once every three weeks beginning with week 1, day 1 |
| Arm B TNBC | Experimental | Drug: Niraparib, Drug: DostarlimabParticipants will be randomized 1:1 to treatment with the combination (Arm B) * 3-week lead-in of niraparib monotherapy followed by treatment with the combination * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 4, day 1 |
| Arm C ER+/HER2- | Experimental | Drug: Niraparib, Drug: Dostarlimabexploratory cohort of estrogen receptor (ER) positive HER2-negative participants will be enrolled to Arm C. * Niraparib Daily beginning with week 1, day 1 * Dostarlimab Once every three weeks beginning with week 1, day 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate in the study. Laboratory assessments for eligibility must be completed within 14 days prior to the date of registration. Diagnostic imaging, such as MRIs and CT scans, must be performed within 28 days of the planned treatment start.
- Participants must have histologically or cytologically confirmed invasive breast cancer Stage I to III with primary tumor size at least 1.0 cm defined by physical exam or imaging (whichever is larger). In the case of a multifocal, multicentric, or bilateral disease, the largest lesion must be ≥ 1.0 cm and designated as the "index" lesion for tumor evaluations. Patients with inflammatory breast carcinoma are not eligible.
- Participants must have documentation of estrogen receptor (ER) and progesterone receptor (PR) testing by IHC according to local institutional guidelines in a CLIA-approved setting. Central confirmation of ER/PR status is not required. All tumors must be HER2 negative.
- Participants must have documented HER2-negative invasive tumor according to local institutional guidelines in a CLIA-approved setting. Central confirmation of HER2 status is not required. HER2 negative is defined as:
- Participants must have documented germline mutation in BRCA1, BRCA2 or PALB2 that is deleterious or suspected to be deleterious (known or predicted to be detrimental/lead to loss of function). Mutation must be identified through a CLIA-approved laboratory. Final determination of eligibility for any discordant results in pathogenicity will be made by the sponsor-investigator. A formal eligibility exception will not be required in these cases as long as approval by overall study PI is granted and documented.
Key exclusion criteria (23 listed)
- Stage IV breast cancer.
- Concurrent therapy with any other investigational product
- Prior treatment for the current breast cancer, including prior chemotherapy, immune therapy, hormonal therapy, radiation, or investigational therapy for this diagnosis.
- Excisional biopsy of the primary tumor and/or excision of axillary lymph nodes, including SLNB, prior to study treatment.
- Participants with a history of malignancy are ineligible except in the following circumstances:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZejulaPredetermined dosage PO Daily | Drug | Arm A Triple Negative Breast Cancer (TNBC), Arm B TNBC, Arm C ER+/HER2- |
| DostarlimabAlso: TSR042Predetermined Dosage, IV,q3 weeks | Drug | Arm A Triple Negative Breast Cancer (TNBC), Arm B TNBC, Arm C ER+/HER2- |
Primary outcome
Change in Tumor-infiltrating Lymphocytes (TILs)
Time frame: baseline to 21 days (cycle 2 day 1)
Change in TILs score from baseline to cycle 2 day 1; the score is estimated by a pathologist according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines, as the percentage (0-100) of the tumor's stromal area occupied by mononuclear immune cells on a stained tissue slide; higher scores generally correlate with improved survival outcomes and better responses to chemotherapy
Pathologic Complete Response (pCR) Rate in TNBC
Time frame: 18 weeks
The number and percentage of participants achieving pCR without additional neoadjuvant therapy; the residual cancer burden (RCB) method as described by Symmans et al. was used to assess response, with increasing RCB score associated with greater burden of residual disease after surgery; RCB-0 reflects pCR (no residual disease), whereas RCB-I, RCB-II, and RCB-III reflect minimal, moderate, and extensive residual disease, respectively
4 secondary outcomes
pCR Rate in ER+/HER2- Breast Cancer
Time frame: 18 weeks
Association Between Change in TILs Score and pCR
Time frame: baseline to 18 weeks
Rate of Residual Cancer Burden (RCB)-0/1 Response
Time frame: 18 Weeks
Treatment-related Adverse Events
Time frame: baseline up to 31 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Related trials for Stage I Breast Cancer
Active, not recruitingPhase 3
Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer
Breast Carcinoma In Situ, Invasive Breast Carcinoma
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
RecruitingPhase 1/2
Phase I/II Study of Intrathecal/Ommaya T-DXd in HER2-Expressing Breast Cancer With Leptomeningeal/Brain Metastases
Breast Cancer
Not yet recruitingPhase 1
A Study to Evaluate YF550 in Participants With Locally Advanced or Metastatic Solid Tumors.
Solid Tumor (Phase I), Ovarian Cancer
RecruitingPhase 1/2
Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
Pancreatic Cancer, Renal Cell Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erica L. Mayer, MD, MPH principal investigator
Dana-Farber Cancer Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib and Dostarlimab in people with Stage I Breast Cancer and Stage II Breast Cancer, run by Dana-Farber Cancer Institute at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Tumor-infiltrating Lymphocytes (TILs) (time frame: baseline to 21 days (cycle 2 day 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.