Niraparib Plus Dostarlimab Demonstrates Meaningful Neoadjuvant Activity in Germline BRCA1/2-Mutated TNBC
Key Clinical Takeaways
- Design/Population: This phase 2 randomized study enrolled 46 patients with germline BRCA1/2–mutated, HER2-negative early triple-negative breast cancer eligible for neoadjuvant therapy. Patients were assigned to receive either upfront niraparib plus dostarlimab or a 3-week niraparib lead-in followed by combination therapy for a total of 18 weeks.
- Key Outcomes: Across both study arms, the pathologic complete response (pCR) rate was 50%, exceeding the predefined efficacy benchmark of greater than 43%. Significant increases in stromal tumor-infiltrating lymphocytes (sTILs) were observed at week 3 in both arms, and higher baseline sTILs were associated with achieving pCR.
- Clinical Relevance: Niraparib combined with dostarlimab produced meaningful antitumor activity with manageable toxicity in patients with germline BRCA–mutated early TNBC. These findings support the potential of a chemotherapy-free neoadjuvant approach and highlight the importance of biomarker-driven selection in this population.
According to results from the phase 2 TBCRC 056 trial, neoadjuvant niraparib plus dostarlimab demonstrated clinically meaningful pathologic complete response (pCR) activity among patients with germline BRCA1/2-mutated triple-negative breast cancer (TNBC).
These findings were presented by Erica Mayer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
In this study, 46 patients with HER2-negative, BRCA1/2-mutated TNBC were randomized to receive either 200 mg of once daily niraparib plus 500 mg of dostarlimab once every 3 weeks for 18 weeks (arm A) or a 3-week niraparib lead-in followed by 15 weeks of niraparib plus dostarlimab (arm B), with tumor biopsies performed at baseline and week 3. Patients with residual disease at the end-of-treatment biopsy were permitted to undergo surgery or receive investigator’s choice of additional preoperative systemic therapy.
The primary end point was pCR and change in stromal tumor-infiltrating lymphocytes (sTILs) from baseline to week 3. Safety served as a key secondary end point.
At analysis, 38 patients completed the planned dostarlimab cycles (mean, 5.1) and 6 cycles of niraparib (mean, 5.7). pCR was achieved in 50% of patients; 26.1% had residual disease and 23.9% crossed over to preoperative systemic therapy. The pCR rate was 50% in both treatment arms, exceeding the predefined efficacy threshold (≤46%). Among patients with evaluable paired biopsies, mean sTILs increased by 11.4% in arm A (P = .009) and by 22.7% in arm B (P = .003). Across all patients, mean baseline sTILs was 15% in those who achieved pCR and 5% in those who did not (P = .03). No association was observed between pCR and baseline PD-L1 score or estrogen receptor status.
The most common grade ≥2 adverse events included anemia (26.1%), fatigue (21.7%), hypertension (15.2%), hypothyroidism (15.2%), and neutropenia (15.2%). The most frequent grade ≥ 3 adverse events were anemia (17%) and neutropenia (6.5%). Dostarlimab was discontinued in 5 patients (3 for inadequate response or progression; 2 for toxicity), and niraparib was discontinued in 7 patients (3 for inadequate response or progression; 4 for toxicity).
“In patients with gBRCAm early TNBC, 18 weeks of targeted therapy using PARP [inhibitor] and anti-PD1 agents, with or without 3-week PARP [inhibitor] lead-in, resulted in a pCR rate of 50% and a statistically significant increase in sTILs from BL to week 3,” concluded Dr Mayer. “Further ongoing correlative work may identify best candidates for this non-chemotherapy-based approach.”
Source:
Mayer E, Graham N, Leon-Ferre RA, et al. Tbcrc 056: a phase 2 study of neoadjuvant niraparib with dostarlimab for patients with BRCA- or PALB2-mutated breast cancer: results from the TNBC cohorts. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract RF5-02
