On June 24, 2026, the U.S. Food and Drug Administration (FDA) approved the antibody-drug conjugate sacituzumab govitecan-hziy (Trodelvy) for two indications in adults with triple-negative breast cancer (TNBC).
The first indication, supported by data from ASCENT-03, is for sacituzumab govitecan-hziy as a single agent for the first-line treatment of adults with unresectable locally advanced or metastatic TNBC who are not candidates for PD-1 or PD-L1 inhibitor–based therapy.
The second indication, supported by data from ASCENT-04/KEYNOTE D-19, is for sacituzumab govitecan-hziy in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the first-line treatment of adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (combined positive score [CPS] ≥ 10) as determined by an FDA-authorized test.
Efficacy and Safety
Efficacy of sacituzumab govitecan-hziy as a single agent for TNBC was evaluated in ASCENT-03 (ClinicalTrials.gov identifier NCT05382299), a multicenter, open-label, randomized trial that enrolled 558 patients with unresectable locally advanced or metastatic TNBC who had not received previous systemic therapy for advanced disease and who were not candidates for PD-1 or PD-L1 inhibitor therapy. Patients were randomly assigned 1:1 to either sacituzumab govitecan-hziy on days 1 and 8 of a 21-day cycle or nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, paclitaxel on days 1, 8, and 15 of a 28-day cycle, or gemcitabine and carboplatin at area under the curve (AUC) 2 on days 1 and 8 of a 21-day cycle (the TPC arm).
The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; additional efficacy outcome measures included overall survival (OS) and confirmed objective response rate (ORR). Median PFS was 9.7 months (95% confidence interval [CI] = 8.1–11.1 months) in the sacituzumab govitecan-hziy arm and 6.9 months (95% CI = 5.6–8.2 months) in the TPC arm (hazard ratio [HR] = 0.62, 95% CI = 0.50–0.77, P < .0001). Confirmed ORR was 50% (95% CI = 44%–56%) and 47% (95% CI – 41%–53%) in the respective arms. OS data were immature.
Efficacy of sacituzumab govitecan-hziy in combination with pembrolizumab was evaluated in ASCENT-04/KEYNOTE-D19 (NCT05382286), a multicenter, open-label, randomized trial that enrolled 443 patients with locally advanced or metastatic TNBC who had not received previous systemic therapy for advanced disease and whose tumor expressed PD-L1 (CPS ≥ 10) according to the PD-L1 IHC 22C3 pharmDx assay. Patients were randomly assigned 1:1 to receive either sacituzumab govitecan-hziy on day 1 and day 8 of a 21-day cycle in combination with pembrolizumab on day 1 of a 21-day cycle or nab-paclitaxel on days 1, 8 and 15 of a 28-day cycle, paclitaxel on days 1, 8 and 15 of a 28-day cycle, or gemcitabine and carboplatin at AUC = 2 on days 1 and 8 of a 21-day cycle in combination with pembrolizumab on day 1 of a 21-day cycle (the TPC plus pembrolizumab arm).
The primary efficacy outcome measure was PFS by BICR per RECIST v1.1; additional efficacy outcome measures included OS and ORR. Median PFS was 11.2 months (95% CI = 9.3–16.7 months) in the sacituzumab govitecan-hziy arm and 7.8 months (95% CI = 7.3–9.3 months) in the TPC plus pembrolizumab arm (HR = 0.65, 95% CI = 0.51–0.84, P = .0009). Confirmed ORR was 61% (95% CI = 55%–68%) and 55% (95% CI = 48%–62%) in the respective arms. OS data were immature.
The prescribing information for sacituzumab govitecan-hziy contains a boxed warning for diarrhea and neutropenia and includes warnings and precautions for hypersensitivity and infusion-related reactions, nausea/vomiting, patients with reduced UGT1A1 activity, and embryo-fetal toxicity.
The prescribing information for pembrolizumab includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Recommended Dosage
The recommended sacituzumab govitecan-hziy dose as a single agent or in combination with pembrolizumab is 10 mg/kg administered as an intravenous infusion on days 1 and 8 of each 21-day cycle. Sacituzumab govitecan-hziy should be continued until disease progression or unacceptable toxicity. Refer to the prescribing information for the recommended dosing information for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Israel’s Ministry of Health, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved these applications 1 month ahead of the FDA goal date.
