A phase 2 study of response-guided neoadjuvant sacituzumab govitecan and pembrolizumab (SG/P) in patients with early-stage triple-negative breast cancer: Results from the NeoSTAR trial.

511 Background: Sacituzumab govitecan (SG) is a TROP-2 directed antibody-drug conjugate (ADC) approved for metastatic triple negative breast cancer (TNBC). Pembrolizumab (P), an anti-programmed death 1 monoclonal antibody, is approved for early-stage TNBC and metastatic PD-L1 positive TNBC. However, safety and efficacy of SG+P in early TNBC is not known. We published results of Arm A1 investigating neoadjuvant SG monotherapy in early TNBC (Spring et al. Annals of Onc 2024). Here we present results from Arm A2 of the NeoSTAR study investigating the combination of neoadjuvant SG + P in early-stage TNBC (NCT04230109). Methods: Patients (pts) with early TNBC (tumor size ≥2 cm or node positive) with no prior treatment were eligible. Pts received SG at starting dose of 10mg/kg on days 1,8 of a 21-day cycle for 4 cycles with P 200 mg given on day 1 of each cycle. After trial regimen, pts underwent imaging to determine residual radiographic disease per RECIST v1.1. A biopsy was performed if residual disease (RD) was suspected. Additional neoadjuvant chemotherapy (ANACT) was at discretion of the treating physician prior to definitive surgery. The primary objective was rate of pathologic complete response (pCR) with neoadjuvant SG/P. Secondary objectives included need for ANACT, radiographic response (RR), safety and tolerability (adverse events [AEs] per CTCAE v5.0) and event-free survival. A Simon two-stage design and standard descriptive statistics were utilized, including 95% binomial confidence intervals for all rates estimated. Results: From 5/19/23-8/13/24, 50 pts were enrolled (median age: 57 years, range 23-77). Clinical anatomic stage was II in 48 pts (96%) and III in 2 pts (4%). 64% of pts were node negative at diagnosis. 44 pts (88%) completed the trial regimen (5 pts had toxicity, 1 pt progressed on treatment). In interim analysis, 5/15 had pCR and so the remaining 35 were enrolled. The pCR rate per protocol (pts with pCR at surgery directly after SG/P without ANCT) was 16/50 (34%, 95% CI 19.5-46.7). The RR rate (complete CR or partial response PR) was 66% (95% CI 50-78%), 30% CR and 36% PR. Of 26 pts who received ANACT, 9 experienced pCR (2 biopsy-confirmed RD, 6 negative or non-diagnostic RD biopsy, 1 no biopsy). Overall, 25 (50%, 95% CI 35.5-64.5) pts had pCR at surgery. Of 5 pts with pathogenic BRCA mutations, 3 (60%) had pCR after SG/P, and 1 pt had pCR after ANACT. 20 pts (40%) had grade 3 or higher AEs. The most common AEs were nausea (28, 56%), alopecia (26, 52%), fatigue (23, 46%), and diarrhea (22, 44%). Dose reductions of SG occurred in 4 pts (8%). Updated survival and biomarker data will be presented at the meeting. Conclusions: In the first trial to investigate the SG/P combination in early TNBC, 34% of pts had pCR. Additional research is needed to determine the optimal duration and sequence of neoadjuvant SG/P and chemotherapy for pts with TNBC. Clinical trial information: NCT04230109 .