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ASCENT-04 / KEYNOTE-D19 — Sacituzumab govitecan + pembrolizumab, 1L PD-L1+ metastatic TNBC

Abstract: LBA1000 (PFS2 / subsequent therapy) · 1013 (biomarker subgroups) · Session: Breast Cancer—Metastatic, oral abstract sessions, ASCO 2026 (abstract 1013 Rapid Oral, Sun May 31, 12:30 PM CT; LBA1000 embargo lifts Tue Jun 2, 7:00 AM CT) · Presenters: Kevin Kalinsky, MD, MS (Winship/Emory) — LBA1000; Sara M. Tolaney, MD, MPH (Dana-Farber/Harvard) — 1013

At a glance

  • Sponsor: Gilead Sciences (Trodelvy) in collaboration with Merck (KEYTRUDA; KEYNOTE-D19)
  • PI / presenter: Kevin Kalinsky (LBA1000); Sara M. Tolaney (1013 biomarker analysis)
  • NCT ID: NCT05382286
  • Phase: 3, randomized, open-label
  • Design: Sacituzumab govitecan + pembrolizumab vs investigator's-choice chemotherapy + pembrolizumab; abstract 1013 = prespecified/exploratory PFS by biomarker subgroup (Trop-2 H-score quartile, tBRCA status, HER2 IHC status)
  • N: 443 (SG+pembro 221; chemo+pembro 222); Trop-2 biomarker analysis set (BAS) subset for subgroup work
  • Primary endpoint(s): PFS by BICR (primary, positive at ASCO 2025 / NEJM Jan 2026); ASCO 2026 = PFS2 / subsequent-therapy update (LBA1000) and biomarker subgroup consistency (1013)
  • Comparator: chemotherapy (investigator's choice) + pembrolizumab — active SOC, not placebo
  • Indication: previously untreated locally advanced unresectable or metastatic TNBC, PD-L1+ (CPS ≥10)
  • Line: first-line

Headline result

Primary PFS (presented ASCO 2025, NEJM Jan 2026) showed median PFS 11.2 vs 7.8 months for SG+pembro vs chemo+pembro (HR 0.65; 95% CI 0.51–0.84; P<0.001), a 35% reduction in progression/death. At ASCO 2026, two follow-on analyses are presented: LBA1000 (Kalinsky) reports PFS2 and outcomes on subsequent lines of therapy, addressing whether the first-line benefit is preserved through the next treatment line; abstract 1013 (Tolaney) shows the PFS benefit is consistent across all biomarker subgroups examined, with no subgroup losing the benefit.

In the biomarker analysis, ITT median PFS was 11.2 vs 7.8 months (HR 0.65; 95% CI 0.51–0.84), and within the Trop-2 biomarker analysis set median PFS was 11.7 vs 7.8 months (HR 0.63; 95% CI 0.48–0.82). By Trop-2 H-score quartile, benefit deepened with higher expression but persisted even at low expression: Q1 9.3 vs 9.0 mo (HR 0.81), Q2 9.6 vs 7.4 mo (HR 0.73), Q3 13.5 vs 8.4 mo (HR 0.46; 95% CI 0.27–0.80), Q4 16.6 vs 9.2 mo (HR 0.57; 95% CI 0.33–0.99). By tBRCA status: wild-type 9.6 vs 7.4 mo (HR 0.67; 0.49–0.91), mutated 16.6 vs 12.9 mo (HR 0.88; 0.45–1.74), overall tBRCA-tested 11.1 vs 7.8 mo (HR 0.69; 0.52–0.91). By HER2 IHC status: IHC 0 16.6 vs 9.0 mo (HR 0.69; 0.46–1.04), HER2-low 11.2 vs 7.7 mo (HR 0.67; 0.48–0.92). Tolaney concluded median PFS was longer with the SG combination across subgroups, supporting broad applicability of the regimen rather than a narrow Trop-2-high-only effect. (Subgroup analyses were not powered for formal significance; p-values not reported.)

Mechanism / class

Sacituzumab govitecan (Trodelvy) is a Trop-2–directed antibody–drug conjugate delivering the SN-38 (topoisomerase-I inhibitor) payload via a hydrolyzable linker; already approved in pretreated metastatic TNBC (ASCENT) and HR+/HER2− metastatic breast cancer (TROPiCS-02). Pembrolizumab is an anti–PD-1 immune checkpoint inhibitor, the established SOC partner with chemotherapy in 1L PD-L1+ (CPS ≥10) metastatic TNBC (KEYNOTE-355). ASCENT-04/KEYNOTE-D19 substitutes SG for chemotherapy alongside checkpoint blockade in the first-line setting.

Discussant takeaway

The 2026 discussion centers on durability of benefit beyond first line: a positive PFS2 (LBA1000) would counter the concern that front-loading SG simply borrows efficacy from later lines, while the biomarker work (1013) argues against restricting SG by Trop-2/HER2/BRCA status. Trade-press framing (OncLive, CancerNetwork) positions the parent ASCENT-04 result as a potential new 1L standard of care, with the biomarker analysis reinforcing that benefit is not confined to Trop-2-high tumors. OS remained immature at the primary readout and is the outstanding confirmatory endpoint.

Practice-changing?

Yes (within PD-L1+ 1L mTNBC), pending mature OS. The primary PFS win already positions SG+pembro as a potential new first-line standard for CPS ≥10 disease; the ASCO 2026 PFS2 and biomarker data reinforce breadth and durability of benefit. The subgroup analysis removes a key barrier to adoption by showing benefit retained across Trop-2 quartiles, BRCA status, and HER2 IHC status, arguing against the need for Trop-2 biomarker selection to deploy the regimen. Confirmatory OS and regulatory action are the remaining gates.

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