131 Primary Results From ASCENT-03: A Randomized Phase 3 Study of Sacituzumab Govitecan (SG) vs Chemotherapy (Chemo) in Patients (pts) With Previously Untreated Advanced Triple-Negative Breast Cancer (TNBC) Who Are Unable to Receive PD-(L)1 Inhibitors (PD-[L]1i)

Background

Significant progression-free survival (PFS) benefit was observed with sacituzumab govitecan vs chemotherapy in pretreated metastatic triple-negative breast cancer (TNBC) (ASCENT) and with sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab in first-line PD-L1 plus metastatic TNBC (ASCENT-04). For patients with metastatic TNBC who cannot receive a PD-L1 inhibitor, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of first-line sacituzumab govitecan vs chemotherapy in patients with locally advanced unresectable or metastatic TNBC who are unable to receive a a PD-L1 inhibitor.

Methods

Patients had centrally confirmed PD-L1−metastatic TNBC (defined as combined positive score [CPS] < 10) or PD-L1 plus metastatic TNBC (CPS ≥ 10) but were unable to receive PD-L1 inhibitor due to a comorbidity or prior use in the curative setting. Randomization (1:1) to sacituzumab govitecan (10 mg/kg intravenously, days 1 & 8 in 21-day cycles) or chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary end points included overall survival (OS), objective response rate and duration of response (DOR) by BICR, and safety.

Results

A total of558 patients (279 in each group) with metastatic TNBC were randomly assigned. With a median follow-up of 13.2 months, sacituzumab govitecan showed a significant improvement in median PFS vs chemotherapy (9.7 vs 6.9 months; HR, 0.62; 95% CI, 0.50-0.78; P <.0001); median DOR was 12.2 months vs 7.2 months (Table). OS data were immature. The most frequent grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (43%) and diarrhea (9%) with sacituzumab govitecan and neutropenia (41%) and anemia (16%) with chemotherapy.

Conclusions

Sacituzumab govitecan led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemotherapy in first-line metastatic TNBC. The safety profile of sacituzumab govitecan was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with sacituzumab govitecan vs chemotherapy. These data support sacituzumab govitecan as a potential new standard of care for patients with previously untreated metastatic TNBC who are unable to receive a PD-L1 inhibitor.