The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending the marketing authorization of 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
A European Commission decision on the indication is anticipated later in 2026.
The CHMP recommendation was based on findings from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286), which were presented at the 2025 ASCO Annual Meeting.1,2 Patients who received sacituzumab govitecan plus pembrolizumab (n = 221) achieved a median progression-free survival (PFS) by blinded independent central review (BICR) of 11.2 months (95% CI, 9.3-16.7) vs 7.8 months (95% CI, 7.3-9.3) among those given chemotherapy plus pembrolizumab (n = 222), translating to a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51-0.84; P < .001).²
“If authorized, [sacituzumab govitecan] plus [pembrolizumab] would build on the recent approval of [sacituzumab govitecan] monotherapy and help establish a [sacituzumab govitecan]-based approach as a first-line treatment option for patients with metastatic TNBC across PD-L1 status,” Evandro de Azambuja, MD, PhD, stated in a news release.¹
De Azambuja is head of the Medical Support Team at the Jules Bordet Institute in Brussels, Belgium, and served as an investigator on ASCENT-04.
Sacituzumab Govitecan Plus Pembrolizumab in Frontline PD-L1–Positive Metastatic TNBC: ASCENT-04 Highlights
- 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 (HR, 0.65; 95% CI, 0.51-0.84; P < .001).
- The ORRs were 60% (95% CI, 52.9%-66.3%) vs 53% (95% CI, 46.4%-59.9%), respectively, and the median DORs were 16.5 months (95% CI, 12.7-19.5) vs 9.2 months (95% CI, 7.6-11.3), respectively.
- The OS data were immature at the time of the analysis; 43% of patients in the chemotherapy arm crossed over to receive sacituzumab govitecan.
How was the ASCENT-04/KEYNOTE-D19 trial designed?
ASCENT-04/KEYNOTE-D19 was an international, open-label trial that randomly assigned 443 patients with previously untreated, PD-L1-positive (CPS ≥ 10 by the 22C3 assay), locally advanced unresectable or metastatic TNBC in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or investigator’s choice of chemotherapy plus pembrolizumab.² Sacituzumab govitecan was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles with pembrolizumab at 200 mg on day 1 of each cycle; chemotherapy options comprised gemcitabine/carboplatin, paclitaxel, or nab-paclitaxel (Abraxane). Randomization was stratified by curative treatment-free interval, geography, and prior exposure to PD-1/PD-L1 inhibition in the curative setting.
PFS by BICR served as the primary end point. Secondary end points included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by BICR, and safety. The trial used a crossover design permitting patients in the chemotherapy arm to receive sacituzumab govitecan following disease progression.¹
What additional efficacy and safety data were reported from ASCENT-04?
The ORR was 60% (95% CI, 52.9%-66.3%) in the sacituzumab govitecan arm vs 53% (95% CI, 46.4%-59.9%) in the chemotherapy arm (OR, 1.3; 95% CI, 0.9-1.9); among responders, the median DORs were 16.5 months (95% CI, 12.7-19.5; n = 132) vs 9.2 months (95% CI, 7.6-11.3; n = 118), respectively.² The OS data were immature at the time of the analysis, however, a positive trend was observed in favor of the sacituzumab govitecan arm, despite the high crossover rate.
Grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 71% of patients treated with sacituzumab govitecan plus pembrolizumab vs 70% of those given chemotherapy plus pembrolizumab. Treatment discontinuation due to TEAEs occurred in 12% and 31% of patients, respectively, and TEAEs leading to death occurred in 3% of patients in each arm. Per the United States prescribing information, the most common adverse reactions occurring in at least 25% of patients treated with the combination in ASCENT-04 were diarrhea, nausea, fatigue, alopecia, constipation, rash, vomiting, abdominal pain, and headache; the most common grade 3/4 laboratory abnormalities reported in at least 25% of patients were decreased neutrophil counts and decreased leukocyte counts.¹
What is the broader regulatory status of sacituzumab govitecan in frontline TNBC?
Sacituzumab govitecan is a TROP-2–directed antibody-drug conjugate consisting of a hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. TROP-2 is expressed in approximately 90% of breast tumors.
In June 2026, the European Commission approved sacituzumab govitecan monotherapy for the treatment of adult patients with unresectable or metastatic TNBC who have not received prior systemic therapy for metastatic disease and who are not candidates for PD-1 or PD-L1 inhibitor therapy, based on data from the phase 3 ASCENT-03 trial (NCT05382299).³ That same month, 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 or pembrolizumab and berahyaluronidase alfa-mph (Keytruda Qlex) for patients whose tumors express PD-L1 with a CPS of 10 or higher as determined by an FDA-authorized test.4
References
- 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 July 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
- Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109
- 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 July 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
- 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 July 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
