Gilead's Trodelvy Secures Broad FDA Approval in First-Line Metastatic TNBC, Escalating TROP2 ADC Market War

Gilead's Trodelvy Secures Broad FDA Approval in First-Line Metastatic TNBC, Escalating TROP2 ADC Market War

On June 24, 2026, the U.S. Food and Drug Administration (FDA) granted a major regulatory expansion to Gilead Sciences' first-in-class TROP2 antibody-drug conjugate (ADC), Trodelvy (sacituzumab govitecan-hziy), approving it for the first-line treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC).

The FDA approved Trodelvy across two distinct indications in the front-line setting:

1. As a monotherapy for patients with TNBC who are not candidates for PD-1/PD-L1 inhibitors. This approval is supported by findings from the Phase 3 ASCENT-03 trial, in which Trodelvy monotherapy demonstrated a 38% reduction in the risk of disease progression or death compared to standard-of-care chemotherapy.
2. In combination with Merck's Keytruda (pembrolizumab) for patients whose tumors express PD-L1 (Combined Positive Score [CPS] $\ge$ 10). This approval is backed by the Phase 3 ASCENT-04 trial (also known as Keynote-D19), which demonstrated a 35% improvement in progression-free survival (PFS) for the Trodelvy-Keytruda combination compared to Keytruda plus chemotherapy.

The TROP2 ADC Competitive Landscape

This approval sets up a high-stakes commercial showdown with Daiichi Sankyo and AstraZeneca's Datroway (datopotamab deruxtecan). Just one month prior, Datroway received FDA approval for first-line TNBC, but only for patients ineligible for PD-1/PD-L1 inhibitors. Gilead’s new approval offers a broader label by including PD-L1-positive patients in combination with Keytruda, whereas AstraZeneca and Daiichi's combination trial (Tropion-Breast05) is not expected to read out until 2027.

While Datroway boasts a unique 21% overall survival (OS) benefit in its Phase 3 Tropion-Breast02 trial for PD-L1-negative patients, Gilead’s ASCENT-03 trial has not yet demonstrated a statistically significant OS benefit due to a high cross-over rate (82% of control-arm patients subsequently received Trodelvy). However, Gilead holds a significant commercial advantage in physician familiarity; Trodelvy was first approved in 2020 for second-line TNBC and has treated over 75,000 patients globally.

"Less than a month after an approval for Daiichi Sankyo and AstraZeneca’s Datroway for front-line TNBC patients who are not candidates for PD-1/L1 inhibitors, the FDA has handed Gilead Sciences’ Trodelvy a rivaling approval that allows the drug to be used regardless of patients’ PD-L1 status.¹" — Fierce Pharma, June 2026

"The new FDA approval for Trodelvy in first-line TNBC now allows the first-in-class TROP2 ADC to be used either alone for patients who aren’t eligible for PD-1/L1 inhibitors or in combination with Merck & Co.’s Keytruda for those with PD-L1-positive tumors, defined as a combined positive score of at least 10." — Fierce Pharma, June 2026