FDA Approves Sacituzumab Govitecan for First-Line TNBC Treatment

The FDA has approved sacituzumab govitecan-hziy (Trodelvy) for 2 distinct first-line indications in adults with triple-negative breast cancer (TNBC): as a single agent for patients who are not candidates for PD-1 or PD-L1 inhibitor–based therapy, and in combination with pembrolizumab (Keytruda) for patients whose tumors express PD-L1 with a combined positive score (CPS) of 10 or higher. Both indications apply to adults with unresectable locally advanced or metastatic disease who have not received prior systemic therapy for advanced TNBC.¹

The monotherapy indication was supported by ASCENT-03 (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.² Patients were randomized 1:1 to sacituzumab govitecan, administered on days 1 and 8 of a 21-day cycle, or to treatment of physician's choice (TPC)—nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin, depending on regimen.

The trial's primary efficacy outcome measure was progression-free survival (PFS) by blinded independent central review per RECIST v1.1, with overall survival (OS) and confirmed objective response rate (ORR) as additional outcome measures. Median PFS was 9.7 months (95% CI, 8.1-11.1) with sacituzumab govitecan vs 6.9 months (95% CI, 5.6-8.2) with TPC (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), respectively. OS data remained immature at the time of analysis.

“I think it will be challenging to interpret [OS], because [the study] did provide crossover drug,” said Sara Tolaney, MD, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, in an interview with Targeted Oncology. “We did see that over 80% of patients that got a subsequent treatment after chemotherapy in the control arm did get sacituzumab. And so I think when you have such a high crossover rate, it may be hard to show [OS) benefit. That’s I'm not sure that we need to wait for maturity of OS here. I think seeing a PFS benefit in my mind is sufficient.”

The combination indication was supported by ASCENT-04/KEYNOTE-D19 (NCT05382286), a separate multicenter, open-label, randomized trial enrolling 443 patients with previously untreated locally advanced or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥ 10) by the PD-L1 IHC 22C3 pharmDx assay.³ Patients were randomized 1:1 to sacituzumab govitecan plus pembrolizumab or to TPC plus pembrolizumab. Median PFS by blinded independent central review was 11.2 months (95% CI, 9.3-16.7) in the sacituzumab govitecan arm vs 7.8 months (95% CI, 7.3-9.3) 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) vs 55% (95% CI, 48-62), respectively. As with the monotherapy trial, OS data had not matured.

Safety

The prescribing information for sacituzumab govitecan includes a boxed warning for diarrhea and neutropenia, along with warnings and precautions for hypersensitivity and infusion-related reactions, nausea and vomiting, reduced UGT1A1 enzyme activity, and embryo-fetal toxicity. The pembrolizumab label separately carries warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications associated with allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

Dosing

The recommended dose of sacituzumab govitecan, whether used as monotherapy or with pembrolizumab, is 10 mg/kg administered by intravenous infusion on days 1 and 8 of each 21-day cycle, continued until disease progression or unacceptable toxicity. Clinicians should consult the full prescribing information for pembrolizumab and pembrolizumab/berahyaluronidase alfa-pmph (Keytruda Qlex) dosing.

Regulatory Pathway

The review was conducted under Project Orbis, an Oncology Center of Excellence initiative enabling concurrent review among international regulators; for this application, the FDA collaborated with Australia's Therapeutic Goods Administration, Israel's Ministry of Health, Brazil's health regulatory agency (ANVISA), Health Canada, and Switzerland's Swissmedic, with reviews ongoing at those agencies. The FDA also used its Assessment Aid review tool and approved the applications one month ahead of the agency's goal date.

Clinical Context

Sacituzumab govitecan, a TROP2–directed antibody-drug conjugate, was already approved for previously treated metastatic TNBC and for HR-positive, HER2-negative metastatic breast cancer;⁴ this action extends its use into the first-line metastatic TNBC setting and establishes a biomarker-defined pathway for combining it with checkpoint inhibition. Together, the 2 trials offer clinicians a regimen tailored to PD-L1 status: combination therapy for CPS-high tumors, and monotherapy for patients who are not candidates for immunotherapy. Longer follow-up will be needed to determine whether the PFS benefit translates into a survival advantage in either setting.

REFERENCES

1. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer. News release. US FDA. June 24, 2026. Accessed June 24, 2026. https://tinyurl.com/3n8bk44p

2. Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer (ASCENT-03). ClinicalTrials.gov. Updated April 4, 2026. Accessed June 24, 2026. https://clinicaltrials.gov/study/NCT05382299

3. 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 June 24, 2026. https://clinicaltrials.gov/study/NCT05382286

4. U.S. FDA approves Trodelvy® in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. February 3, 2023. Accessed February 3, 2023. https://www.bwnews.pr/3Rzki2W2