The European Commission’s (EC) approval of sacituzumab govitecan plus pembrolizumab for PD-L1-positive metastatic triple-negative breast cancer (mTNBC) hinges on findings from the phase 3 ASCENT-04 trial, which demonstrated a 35% reduction in disease progression or death compared to chemotherapy plus pembrolizumab. The regimen achieved a median progression-free survival (PFS) of 11.2 months versus 7.8 months, with objective response rates of 61% versus 55%, according to the European Commission. The FDA echoed these findings in its June 24, 2026, approval, citing the same trial data to support the combination as a first-line treatment for patients with PD-L1 expression of at least 10.
European Commission Approves Sacituzumab Govitecan Plus Pembrolizumab for Frontline
The ASCENT-04 trial enrolled 443 patients with previously untreated, locally advanced or metastatic TNBC, randomly assigning them to either the investigational regimen or chemotherapy plus pembrolizumab. The trial’s primary endpoint was PFS by blinded independent central review (BICR), with secondary endpoints including overall survival (OS) and safety. While OS data remained immature at the time of analysis, the significant improvement in PFS and response rates prompted regulatory action from both the EC and FDA. The trial was conducted under the trial identifier NCT05382286.
The safety profile of sacituzumab govitecan plus pembrolizumab included common adverse effects such as diarrhea, nausea, and fatigue, with serious adverse reactions occurring in 38% of patients. The regimen carries boxed warnings for severe neutropenia and diarrhea, per the FDA’s prescribing information. The EC’s decision followed a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on July 24, 2026, highlighting the alignment between European and U.S. regulatory assessments.
The FDA’s approval also included a separate indication for sacituzumab govitecan as a monotherapy for patients ineligible for PD-1/PD-L1 inhibitor therapy, based on the ASCENT-03 trial. This dual approval underscores the drug’s versatility in treating mTNBC across different patient subsets, with the combination therapy targeting PD-L1-positive cases and the monotherapy addressing those without PD-1/PD-L1 eligibility. The ASCENT-03 trial, conducted under NCT05382299, enrolled 558 patients with unresectable locally advanced or metastatic TNBC who had not received previous systemic therapy for advanced disease and were not candidates for PD-1 or PD-L1 inhibitor therapy.
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The ASCENT-03 trial randomized patients (1:1) to either sacituzumab govitecan-hziy on Days 1 and 8 of a 21-day cycle or a chemotherapy regimen of nab-paclitaxel, paclitaxel, or gemcitabine and carboplatin (the TPC arm). Median PFS was 9.7 months (95% CI: 8.1, 11.1) in the sacituzumab govitecan-hziy arm versus 6.9 months (95% CI: 5.6, 8.2) in the TPC arm (Hazard ratio 0.62 [95% CI: 0.50, 0.77]; p-value <0.0001). Confirmed objective response rates were 50% (95% CI: 44, 56) and 47% (95% CI: 41, 53) in the respective arms. OS data remained immature at the time of analysis.
The EC’s approval of sacituzumab govitecan monotherapy on June 23, 2026, followed the same date as the combination therapy approval. This decision was based on data from the phase 3 ASCENT-03 trial, which demonstrated a statistically significant improvement in PFS compared to chemotherapy. The EC’s approval of the combination therapy was also preceded by a June 23, 2026, regulatory decision for the monotherapy indication, underscoring the drug’s expanding role in mTNBC treatment. 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: The approval of [sacituzumab govitecan] plus [pembrolizumab] represents a meaningful advance in the treatment of patients with PD-L1-positive metastatic TNBC [mTNBC],
adding that 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.
The design of the ASCENT-04 trial included 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. Patients were randomly assigned 1:1 to receive 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. The trial’s primary endpoint was PFS by BICR, with secondary endpoints including OS and safety.
FDA approves sacituzumab govitecan-hziy as monotherapy and in combination
The FDA’s approval of sacituzumab govitecan-hziy also included a second indication for the combination with pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the first-line treatment of PD-L1-positive mTNBC. This dual approval highlights the drug’s adaptability to different therapeutic strategies, though the specific trial data for the Keytruda Qlex combination were not detailed in the sources. The FDA’s decision emphasized the importance of PD-L1 testing, requiring patients to have tumors expressing PD-L1 with a combined positive score (CPS) of 10 or higher as determined by an FDA-authorized test.
The EMA’s evaluation of the drug’s safety and efficacy aligned with the FDA’s findings.
