The NeoSTAR trial is the first study to evaluate the combination of sacituzumab govitecan and pembrolizumab as neoadjuvant therapy for patients with early-stage TNBC, building on prior results from SG monotherapy in Arm A1.

Among 50 patients who received sacituzumab govitecan plus pembrolizumab, 24 had no suspected residual disease; at the time of surgery, 16 experienced a pathologic complete response (pCR) after sacituzumab govitecan plus pembrolizumab only (32%), while 8 had residual disease. Of 26 patients with suspected residual disease following the initial 4 cycles who received additional neoadjuvant chemotherapy, 17 experienced residual disease, and 9 achieved a pCR after sacituzumab govitecan plus pembrolizumab and additional chemotherapy. The most common additional therapies included platinum agents (98%) and taxanes (98%).

In a subgroup analysis, the pCR rate was 32.0% across the overall population (n = 50), 33.3% for those with stage II disease (n = 48), and 0.0% (95% CI, 0.0%-84.2%) for those with Stage III disease (n = 2). Additionally, the pCR rates were 11.1% and 43.8% in the node-positive (n = 18) and node-negative (n = 32) groups, respectively, as well as 60.0% in those with BRCA-mutated disease (n = 5). Data also showed a pCR rate of 37.5% in the estrogen receptor (ER)–low group (n = 8) and 31.0% (95% CI, 17.6%-47.1%) in the ER-negative group (n = 42). The treatment achieved an 18-month event-free survival rate of 90.6% and a radiographic response rate of 66%.

Treatment yielded an 18-month event-free survival (EFS) of 90.6%. Results showed a radiographic response rate (RRR) of 66%, with complete responses (CRs) in 30% and partial responses (PRs) in 36% of patients.

In terms of Safety: The most common pembrolizumab-associated toxicities included hypothyroid events (16.0%), colitis (8.0%), and dermatitis (2.0%). Toxicities related to sacituzumab govitecan included alopecia (48.0%), neutropenia (38.0%), nausea (32.0%), and diarrhea (20.0%). The regimen was generally tolerable, with manageable toxicity. Further research is necessary to optimize the duration and sequence of sacituzumab govitecan/pembrolizumab and chemotherapy in this patient population.

KOL insights: 

“In the first trial to investigate the [sacituzumab govitecan/pembrolizumab] combination in early TNBC, 32% of patients experienced pCR after 4 cycles of [sacituzumab govitecan/pembrolizumab]. There were no new safety signals identified, with few patients experiencing dose reductions or treatment discontinuation.”– Expert Opinion.

Conclusion:

About 10% of breast cancers in the US are triple-negative, and are generally more difficult to treat than other subtypes because they do not have many of the most common biomarkers that can be used to guide treatment. TNBC tumors are often larger, and the disease has high rates of disease recurrence at distant sites. 

At ASCO 2025, significant progress in treating triple-negative breast cancer (TNBC) was highlighted, particularly regarding the combination of TRODELVY and KEYTRUDA.  Gilead Sciences' TROP2-targeting drug TRODELVY is already used as a third-line treatment for PD-L1-positive triple-negative breast cancer (TNBC), but could be heading for use in early-stage.

The NeoSTAR Arm A2 trial offers the first prospective evidence supporting sacituzumab govitecan plus pembrolizumab as neoadjuvant therapy in early-stage TNBC. A pCR rate of 34% was achieved with SG/P alone, rising to 50% with the addition of standard chemotherapy, suggesting a potential benefit of sequential treatment. These findings highlight sacituzumab govitecan/pembrolizumab as an active regimen and support further investigation into its optimal sequencing, duration, and integration with systemic therapies. Upcoming biomarker and survival analyses will be key to refining patient selection and therapeutic strategies.