Sacituzumab Govitecan Plus Pembrolizumab Displays Activity in Early-Stage TNBC

Sacituzumab govitecan plus pembrolizumab in TNBC

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Neoadjuvant sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) was effective and showed no new safety signals in patients with early-stage triple-negative breast cancer (TNBC), according to data from arm A2 of the phase 2 NeoSTAR study (NCT04230109) presented during the 2025 ASCO Annual Meeting.1

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% (95% CI, 19.5%-46.7%) across the overall population (n = 50), 33.3% (95% CI, 20.4%-48.4%) 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% (95% CI, 1.4%-34.7%) and 43.8% (95% CI, 26.4%-62.3%) in the node-positive (n = 18) and node-negative (n = 32) groups, respectively, as well as 60.0% (95% CI, 14.7%-94.7%) in those with BRCA-mutated disease (n = 5). Data also showed a pCR rate of 37.5% (95% CI, 8.5%-75.5%) 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).

Treatment yielded an 18-month event-free survival (EFS) of 90.6% (95% CI, 89.2%-100.0%). Results showed a radiographic response rate (RRR) of 66% (95% CI, 50%-78%), with complete responses (CRs) in 30% and partial responses (PRs) in 36% of patients.

“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,” lead study author Rachel Abelman, MD, a medical oncologist at Massachusetts General Hospital Cancer Center, stated in the presentation.1 “Our ongoing translational analysis seeks to identify mechanisms and biomarkers associated with response to [sacituzumab govitecan/pembrolizumab].”

At baseline, patients with at least stage T2 and/or node-positive early TNBC were assigned to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 plus pembrolizumab at 200 mg on day 1 of a 21-day cycle for 4 cycles. Following imaging at week 12, patients with suspected residual disease underwent research biopsy and received additional neoadjuvant chemotherapy of investigator’s choice before surgery. Patients without suspected residual disease underwent surgery; those with a pCR received 4 cycles of a taxane plus carboplatin with pembrolizumab every 3 weeks for 1 year, while those without a pCR received adjuvant therapy based on investigator’s choice.

The study’s primary end point was pCR with neoadjuvant sacituzumab govitecan plus pembrolizumab. Secondary end points included the need for additional neoadjuvant chemotherapy, RRR, 2-year EFS, and safety and tolerability.

Patients 18 years and older with histologically confirmed invasive breast cancer and a primary tumor of 1 cm or greater per radiological imaging were eligible for enrollment on the trial.2 Other eligibility criteria included having an ECOG performance status of 0 or 1 and adequate bone marrow and organ function.

The median age at diagnosis was 57 years (range, 23-77), and most patients had stage II disease (96%). Additionally, most had stage T2 disease (84%), node-negative disease (64%), no germline BRCA mutations (80%), and ER-negative disease (84%).

Overall, 88% (n = 44) of patients completed the study regimen, 10% (n = 5) stopped due to toxicity, and 2% (n = 1) terminated treatment due to progression. Dose reductions and holds were necessary for 8% and 24% of patients, respectively, while investigators administered growth factor therapy to 26% of patients.

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%).

According to the study authors, limitations of the study included the fact that investigators had the discretion to administer additional neoadjuvant chemotherapy if residual disease status was uncertain, which meant that the pCR rate following sacituzumab govitecan/pembrolizumab alone may have been underreported. Additionally, investigators had the discretion to choose adjuvant chemotherapy among those with residual disease at surgery.

References

1. Abelman R, McLaughlin S, Fell G, et al. 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. J Clin Oncol. 2025;43(suppl 16):511. doi:10.1200/JCO.2025.43.16_suppl.511
2. Sacituzumab govitecan In TNBC (NeoSTAR). ClinicalTrials.gov. Updated March 19, 2024. Accessed June 1, 2025. https://tinyurl.com/29w4rpew