On 22 April 2025, Gilead Sciences announced positive topline results from the Phase III ASCENT-04/KEYNOTE-D19 trial. The study evaluated Trodelvy (sacituzumab govitecan-hziy) in combination with Keytruda (pembrolizumab) versus Keytruda plus chemotherapy in patients with previously untreated, PD-L1 positive metastatic or locally advanced triple-negative breast cancer (mTNBC). Tumours in the enrolled patients expressed PD-L1 at a Combined Positive Score (CPS) of 10 or more.

The trial met its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the combo of Trodelvy plus Keytruda compared with the control arm (Keytruda + chemotherapy).

Some key details:

• 443 patients were randomised globally
• The combination’s safety profile was consistent with what is already known for each drug separately. No new safety signals were found
• Overall survival (OS), a secondary endpoint, was still immature when data were cut-off. However a trend favoring improvement was observed. Further follow-up is ongoing

This result is notable for several reasons.

First, triple-negative breast cancer remains one of the hardest subtypes to treat, especially in the first-line metastatic setting. Limited options exist, particularly for patients whose tumours express PD-L1. By combining an antibody-drug conjugate (ADC) with immunotherapy, this study suggests that it may be possible to improve outcomes beyond what checkpoint inhibition plus chemotherapy has achieved.

Second, the findings could shift standard practice if regulatory authorities accept these data and if longer follow-up confirms the survival benefit and manageable toxicity. Clinicians will be particularly attentive to how the PFS gain translates into quality of life, tolerability, and the cost-benefit balance for patients.

Third, this fits into a broader trend where combining targeted or conjugated agents with IO (immuno-oncology) is becoming more common, especially for aggressive cancers. These combinations may enable stronger tumour control earlier in treatment, potentially delaying progression, reducing disease burden, and improving patient outcomes.

Some open questions remain:

• How large was the PFS gain in absolute terms (months), and how did subgroups do (age, ethnicity, performance status, etc.)? These details will be essential for clinicians.
• What was the duration of response (how long patients stayed on benefit) and what was the hazard ratio?
• What were the adverse events in detail, especially immune-related ones, hematologic toxicities, or overlapping toxicities of ADC and immunotherapy?
• Will these results be sufficient for regulatory submission or guideline changes, and how quickly might that happen?

Overall, the ASCENT-04/KEYNOTE-D19 result is a compelling piece of evidence that the Trodelvy + Keytruda combo could offer an important new option for first-line treatment of PD-L1 positive mTNBC. If subsequent data confirm these early findings, patients might see this regimen becoming part of standard care in the near future.