Neoadjuvant low-dose carboplatin and docetaxel in combination with toripalimab for early or locally advanced triple-negative breast cancer (NeoTOP): A single-arm phase 2 trial.

589 Background: Neoadjuvant immunotherapy combined with chemotherapy improves the rate of pathological complete response (pCR) and prognosis of triple-negative breast cancer (TNBC). However, chemo-immunotherapy treatment is frequently associated with adverse events, resulting in dose reduction and delays. Approaches to deescalate chemo-immunotherapy without compromising outcomes for TNBC patients are needed. Evidence suggests that low-dose carboplatin potentiates the anti-tumor effect of PD-1 inhibitors through many mechanisms. The NeoTOP trial aimed to assess the efficacy and safety of low-dose carboplatin and docetaxel in combination with toripalimab as neoadjuvant therapy for early or locally advanced TNBC. Methods: This is a single-arm, open-label, phase 2 trial. Patients with untreated stage IIA-IIIC TNBC were enrolled. Eligible patients received carboplatin (AUC=4), docetaxel (75 mg/m 2 ) and toripalimab (240 mg), every 21 days for a total of 6 cycles. Toripalimab (240mg, every 3 weeks) continued post-operatively for a further 11 cycles. The primary endpoint was the rate of pCR (ypT0/Tis ypN0). The secondary endpoints included safety, objective response rate (ORR), residual cancer burden (RCB) rate, event-free survival and overall survival. This study used Simon’s two-stage design. Results: From January 2022 to September 2024, 51 patients were enrolled. Among them, 29 patients (56.9%) had stage II, and 22 (43.1%) had stage III. Four patients prematurely discontinued study treatment due to adverse events (three patients) or tumor progression (one patient), including two discontinued toripalimab only and two discontinued both toripalimab and chemotherapy. One of the four patients who discontinued treatment achieved a pCR when proceeding to surgery. One patient achieved clinical CR after neoadjuvant therapy and refused to receive surgery. After surgery, pCR in both breast and lymph nodes was achieved in 29 of 50 patients, resulting in a pCR rate of 58.0%. For all the 51 patients who received at least one dose of neoadjuvant therapy, the ORR was 90.2%. The proportions of RCB-0, RCB-1, RCB-2, and RCB-3 were 58%, 12%, 22%, and 8%. All 51 (100%) patients reported any grade of treatment-related adverse events (TRAEs). Grade ≥3 TRAEs occurred in 23 (45.1%) patients. Serious adverse events were reported in 5 (9.8%) patients. The regimen was well tolerated, and no new toxicity signals were noted. Conclusions: The combination of low-dose carboplatin, docetaxel, and toripalimab showed promising efficacy and manageable safety, suggesting the feasibility of this regimen in the neoadjuvant setting for TNBC. Further randomized phase III trials are warranted. Clinical trial information: NCT06618014 .