News|Articles|August 24, 2026

European Commission Approves Sacituzumab Govitecan Plus Pembrolizumab for Frontline PD-L1+ mTNBC

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Key Takeaways

Indication targets adults with unresectable locally advanced/metastatic TNBC, no prior metastatic systemic therapy, and PD-L1 CPS ≥10 for the combination; monotherapy is reserved for PD-(L)1-ineligible patients.
Efficacy favored sacituzumab govitecan–pembrolizumab with PFS HR 0.65 and median 11.2 months versus 7.8 months; ORR increased to 61% versus 55%.
ASCENT-04 randomized patients 1:1 to sacituzumab govitecan 10 mg/kg days 1/8 every 21 days plus pembrolizumab 200 mg day 1, versus chemotherapy plus pembrolizumab.
Primary end point was BICR-assessed PFS; OS, ORR, duration of response, safety, and quality of life were secondary, with OS data immature at the reported analysis.
Safety signals included frequent diarrhea/nausea and hematologic toxicity; serious AEs occurred in 38%, discontinuations in 7%, fatalities in 3.2%, and boxed warnings underscore neutropenia and severe diarrhea.

The European Commission approved sacituzumab govitecan plus pembrolizumab for treatment-naive, PD-L1-positive metastatic triple-negative breast cancer.

The European Commission (EC) has granted marketing authorization to sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) for the treatment of adult patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score (CPS) of 10 or higher.¹

This approval was based on findings from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286). Findings showed that the median progression-free survival (PFS) by blinded independent central review (BICR) was 11.2 months (95% CI, 9.3-16.7) with sacituzumab govitecan plus pembrolizumab vs 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab (HR, 0.65; 95% CI, 0.51-0.84; P = .0009).² The respective objective response rates (ORRs) were 61% (95% CI, 55%-68%) and 55% (95% CI, 48%-62%). The overall survival (OS) data were immature at the time of the analysis.

The decision follows the June 23, 2026, EC approval of sacituzumab govitecan monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic disease and who are not candidates for PD-1/PD-L1 inhibitor therapy.³ This regulatory decision was based on data from the phase 3 ASCENT-03 trial (NCT05382299).

“The approval of [sacituzumab govitecan] plus [pembrolizumab] represents a meaningful advance in the treatment of patients with PD-L1-positive metastatic TNBC [mTNBC],” Evandro de Azambuja, MD, PhD, head of the Medical Support Team at the Jules Bordet Institute in Brussels, Belgium, and an investigator of the ASCENT-04 study, stated in a news release.¹ “This regimen helps redefine a standard of care by offering a novel first-line treatment option for a metastatic patient population with a particularly aggressive form of breast cancer.”

What was the design of ASCENT-04?

This trial enrolled patients with previously untreated, locally advanced or metastatic TNBC who had at least a 6-month interval since their last treatment in the curative setting.⁴ Patients were randomly assigned 1:1 to be treated with intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle, in combination with pembrolizumab at 200 mg on day 1 of each cycle; or chemotherapy in combination with investigator’s choice of paclitaxel, nab-paclitaxel (Abraxane), or gemcitabine plus carboplatin, plus pembrolizumab at the same dose and schedule.

Sacituzumab Govitecan Plus Pembrolizumab in Frontline PD-L1+ Metastatic TNBC: ASCENT-04 Highlights

The investigational regimen reduced the risk of disease progression or death by 35% vs chemotherapy plus pembrolizumab (HR, 0.65; 95% CI, 0.51-0.84; P = .0009).

The median PFS by BICR was 11.2 months (95% CI, 9.3-16.7) with sacituzumab govitecan plus pembrolizumab vs 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab.

The ORRs were 61% (95% CI, 55%-68%) vs 55% (95% CI, 48%-62%), respectively.

PFS by BICR served as the primary end point. Secondary end points included OS, ORR, and duration of response per BICR, as well as safety and quality of life.

What is the safety profile of sacituzumab govitecan plus pembrolizumab?

The most common adverse effects (AEs) occurring in at least 25% of patients treated with sacituzumab govitecan plus pembrolizumab in the ASCENT-04 trial were diarrhea, nausea, fatigue, alopecia, constipation, rash, vomiting, abdominal pain, and headache.¹ The most frequent serious adverse reactions occurring in at least 2% of patients were febrile neutropenia (7%); neutropenia (6%); diarrhea (5%); and fatigue and pneumonia (2.3% each).

Serious AEs occurred in 38% of patients, and 7% discontinued sacituzumab govitecan due to AEs. Fatal AEs occurred in 3.2% of patients. The United States prescribing information for sacituzumab govitecan includes a boxed warning for severe or life-threatening neutropenia and severe diarrhea.

How does the EC approval of sacituzumab govitecan plus pembrolizumab fit into the mTNBC treatment landscape?

The EC decision follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use, which recommended the regimen for this indication on July 24 2026.⁵

Additionally, on June 24, 2026, the FDA approved sacituzumab govitecan for the first-line treatment of unresectable, locally advanced or metastatic TNBC, both as a single agent for patients who are not candidates for PD-1/PD-L1 inhibitor–based therapy and in combination with pembrolizumab for patients whose tumors express PD-L1 with a CPS of 10 or higher.²

References

European Commission expands role of Gilead’s Trodelvy in first-line metastatic triple-negative breast cancer across PD-L1 status. News release. Gilead Sciences, Inc. August 24, 2026. Accessed August 24, 2026. https://www.gilead.com/news/news-details/2026/european-commission-expands-role-of-gileads-trodelvy-in-first-line-metastatic-triple-negative-breast-cancer-across-pd-l1-status
FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer. FDA. June 24, 2026. Accessed August 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line?utm_medium=email&utm_source=govdelivery
European Commission approves Trodelvy as a first-line treatment for metastatic triple-negative breast cancer patients not candidates for PD-(L)1 inhibitors. News release. Gilead. June 23, 2026. Accessed August 24, 2026. https://investors.gilead.com/news/news-details/2026/European-Commission-Approves-Trodelvy-as-a-First-Line-Treatment-for-Metastatic-Triple-Negative-Breast-Cancer-Patients-Not-Candidates-for-PD-l1-Inhibitors/default.aspx
Study of sacituzumab govitecan-hziy and pembrolizumab versus treatment of physician's choice and pembrolizumab in patients with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer (ASCENT-04). ClinicalTrials.gov. Updated September 18, 2025. Accessed August 24, 2026. https://clinicaltrials.gov/study/NCT05382286
CHMP recommends Gilead’s Trodelvy plus Keytruda in PD-(L)1-positive first-line metastatic triple-negative breast cancer. News release. Gilead Sciences, Inc. July 24, 2026. Accessed August 24, 2026. https://investors.gilead.com/news/news-details/2026/CHMP-Recommends-Gileads-Trodelvy-Plus-Keytruda-in-PD-L1-Positive-First-Line-Metastatic-Triple-Negative-Breast-Cancer/default.aspx