Clinical Summary:

• Design/Population: Exploratory biomarker analysis from the phase 3 ASCENT-04 trial evaluating sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in previously untreated PD-L1–positive metastatic triple-negative breast cancer.
• Key Outcomes: Progression-free survival benefits with sacituzumab govitecan plus pembrolizumab were observed across all evaluated biomarker subgroups, including TROP2-high and TROP2-low tumors, BRCA-mutated and BRCA wild-type disease, and HER2-low and HER2 IHC 0 tumors.
• Clinical Relevance: These findings suggest that the efficacy of sacituzumab govitecan plus pembrolizumab is broadly applicable and does not depend on TROP2, BRCA, or HER2 biomarker status.

Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses exploratory biomarker analyses from the phase 3 ASCENT-04 study evaluating sacituzumab govitecan plus pembrolizumab in patients with previously untreated PD-L1–positive metastatic triple-negative breast cancer. The analyses examined whether TROP2 expression, BRCA mutation status, or HER2 expression influenced clinical benefit from the regimen.

Results demonstrated consistent benefit with sacituzumab govitecan plus pembrolizumab across all biomarker-defined subgroups, including patients with low TROP2 expression, BRCA wild-type disease, and HER2 IHC 0 tumors. These findings reinforce the broad activity of the regimen and support its use as a frontline treatment option irrespective of molecular subgroup.

Dr Tolaney presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript: 

At ASCO this year, we presented results from the ASCENT-04 study looking at biomarkers and their association with outcomes within the trial.

ASCENT-04 was a randomized phase3 study evaluating sacituzumab govitecan (SG)  plus pembrolizumab compared with chemotherapy plus pembrolizumab in patients with previously untreated PD-L1–positive metastatic triple-negative breast cancer. The trial had already demonstrated a statistically significant and clinically meaningful improvement in progression-free survival favoring SG plus pembrolizumab compared with chemotherapy plus pembrolizumab.

In this analysis, we looked at exploratory biomarker associations with outcomes. The biomarkers evaluated included TROP2 expression, which was measured by immunohistochemistry. We also looked at BRCA mutation status, which was assessed by whole-exome sequencing of tumor tissue. In addition, we evaluated HER2 status, which was centrally tested by immunohistochemistry with reflex ISH testing when appropriate.

What we found was that the benefit of SG plus pembrolizumab was observed across all levels of TROP2 expression. Whether patients had TROP2-high or TROP2-low tumors, SG plus pembrolizumab consistently performed better than chemotherapy plus pembrolizumab. Similarly, when looking at BRCA mutation status, benefit was observed regardless of whether patients had a BRCA mutation or were BRCA wild-type, again favoring SG plus pembrolizumab over chemotherapy plus pembrolizumab.

We also found that SG plus pembrolizumab outperformed chemotherapy plus pembrolizumab across all HER2 expression groups. Whether tumors were HER2-low or HER2 IHC 0, outcomes consistently favored SG plus pembrolizumab.

Overall, these results support the finding that SG plus pembrolizumab performs better than chemotherapy plus pembrolizumab regardless of TROP2 expression, BRCA mutation status, or HER2 expression level. Taken together, these data further support the use of SG plus pembrolizumab in the first-line treatment of PD-L1–positive metastatic triple-negative breast cancer.

Source: 

Tolaney S, Schmid P, de Azambuja E, et al. ASCENT-04: Analysis of efficacy by biomarker subgroups with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in participants (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 1013.