FDA Approves Sacituzumab Govitecan Monotherapy and In Combination With Pembrolizumab in Frontline TNBC

The FDA has approved sacituzumab govitecan-hziy (Trodelvy) for 2 indications in adults with triple-negative breast cancer (TNBC). The first indication is for sacituzumab govitecan monotherapy 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 is for sacituzumab govitecan plus 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.¹

The monotherapy indication was supported by data from the phase 3 ASCENT-03 trial (NCT05382299). Data from ASCENT-03 revealed that patients who received sacituzumab govitecan achieved a median progression-free survival (PFS) of 9.7 months (95% CI, 8.1-11.1) vs 6.9 months (95% CI, 5.6-8.2) among patients who received chemotherapy (HR, 0.62; 95% CI, 0.50-0.77; P < .0001). The respective confirmed overall response rates (ORRs) were 50% (95% CI, 44%-56%) and 47% (95% CI, 41%-53%) in the respective arms. Overall survival (OS) data were immature at the time of the approval.

The combination indication was informed by data from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286). The median PFS among patients in the sacituzumab govitecan arm was 11.2 months (95% CI, 9.3-16.7) compared with 7.8 months (95% CI, 7.3-9.3) in the control arm, which comprised physician’s choice of chemotherapy plus pembrolizumab (HR, 0.65; 95% CI, 0.51-0.84; P = .0009). The confirmed ORRs were 61% (95% CI, 55%-68%) and 55% (95% CI, 48%-62%), respectively. OS data were immature.

The prescribing information of sacituzumab govitecan includes a boxed warning for diarrhea and neutropenia, and it includes warnings and precautions for hypersensitivity and infusion-related reactions, nausea/vomiting, patients with reduced UGT1A1 activity, and embryo-fetal toxicity.

The prescribing information of pembrolizumab contains warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The recommended monotherapy dose of sacituzumab govitecan 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 should be continued until disease progression or unacceptable toxicity.

“[The approval of] sacituzumab govitecan plus pembrolizumab for our patients with first-line metastatic TNBC is very impactful. This particular subtype of disease is the hardest subtype to treat, and we know that OS for our patients with metastatic TNBC, unfortunately, is quite limited. Seeing advancements for these patients is very critical. The data that we've seen with the combination are a significant improvement, and a clinically meaningful one,” Sara M. Tolaney, MD, MPH, said in an exclusive interview with OncLive^®.

Tolaney is the chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women's Cancers, and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

How was ASCENT-03 designed?

ASCENT-03 enrolled patients with treatment-naive, locally advanced inoperable or metastatic TNBC who are not suitable candidates for treatment with PD-L(1) inhibitors.²

Elibile patients were randomly assigned 1:1 to receive intravenous (IV) sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle or chemotherapy. Patients in the chemotherapy arm were treated with paclitaxel, nab-paclitaxel (Abraxane), or gemcitabine plus carboplatin. Treatment in both arms continued until disease progression per blinded independent central review (BICR) or unacceptable toxicity.

The primary end point was PFS per BICR. Secondary end points included OS, ORR, and duration of response (DOR) per BICR, as well as safety and quality of life (QOL). Exploratory end points included time to second disease progression (PFS2), time to first subsequent therapy (TFST), and time to second subsequent therapy (TSST).

How was ASCENT-04 designed?

ASCENT-04 enrolled patients with untreated, locally advanced or metastatic TNBC.³ Patients were also required to have a PD-L1 CPS of at least 10 and have an interval of at least 6 months since the last treatment in the curative setting. Prior anti–PD-(L)1 therapy use was permitted.

Patients were randomly assigned 1:1 to receive IV sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle plus pembrolizumab or chemotherapy with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin, in combination with pembrolizumab. Pembrolizumab was administered at a dose of 200 mg on day 1 of each 21-day cycle.

The primary end point was PFS per BICR. Secondary end points included OS, ORR, and duration of response (DOR) per BICR, as well as safety and quality of life (QOL). Exploratory end points included PFS2, TFST, and TSST.

How were the safety data in ASCENT-03 and ASCENT-04?

In ASCENT-03, any-grade treatment-emergent adverse effects (TEAEs) were reported at rates of 99% and 97% in the sacituzumab govitecan (n = 275) and chemotherapy (n = 276) arms. Grade 3 or higher TEAEs (66% vs 62%), treatment-related TEAEs (61% vs 53%), as well as TEAEs leading to treatment discontinuation (4% vs 12%), dose interruption (66% vs 62%), dose reduction (37% vs 45%), and death (3% vs < 1%) were reported in both arms. Treatment-emergent serious adverse effects (SAEs) were reported at respective rates of 26% and 24%; 17% and 13% of these respective events were deemed to be treatment-related.

In ASCENT-04, any-grade TEAEs were reported at rates of 99% and 97% in the sacituzumab govitecan plus pembrolizumab (n = 221) and chemotherapy plus pembrolizumab (n = 220) arms. Grade 3 or higher TEAEs (71% vs 70%), as well as TEAEs leading to treatment discontinuation (12% vs 31%), dose interruption (77% vs 74%), dose reduction (35% vs 33%), and death (3% vs 3%) were reported in both arms. Treatment-emergent SAEs were reported at respective rates of 38% and 31%; 28% and 19% of these respective events were deemed to be treatment-related.

What additional efficacy data have been reported for sacituzumab govitecan in frontline TNBC?

Additional efficacy data from ASCENT-03 that were presented during the 2026 ASCO Annual Meeting revealed that the median PFS2 in the sacituzumab govitecan arm (n = 279) was 18.2 months (95% CI, 15.9-not reached [NR]) compared with 14.0 months (95% CI, 12.5-17.4) in the chemotherapy arm (stratified HR, 0.70; 95% CI, 0.55-0.90).² The 12-month PFS2 rates were 71% (95% CI, 65%-76%) and 59% (95% CI, 53%-65%), respectively; the respective 18-month PFS2 rates were 52% (95% CI, 45%-59%) and 41% (95% CI, 33%-48%).

In ASCENT-04, the median PFS2 values in the sacituzumab govitecan plus pembrolizumab (n = 221) and chemotherapy plus pembrolizumab (n = 222) arms were NR (95% CI, NR-NR) and 21.0 months (95% CI, 16.0-NR), respectively (stratified HR, 0.67; 95% CI, 0.48-0.95).³ The 12-month PFS2 rates were 71,9% (95% CI, 64.5%-78.0%) and 53.0% (95% CI, 44.5%-60.8%), respectively; the respective 18-month PFS2 rates were 63.7% (95% CI, 51.1%-73.9%) and 45.6% (95% CI, 35.6%-55.1%).

References

1. 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 June 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
2. Hurvitz SA, Cortes J, Tolaney SM, et al. Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-03 study of participants (pts) with previously untreated metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) vs chemotherapy (chemo). J Clin Oncol. 2026;44(suppl 16):1001. doi:10.1200/JCO.2026.44.16_suppl.1001
3. Kalinsky K, Schmid P, de Azambuja E, et al. Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-04 study of participants (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) plus pembrolizumab (pembro) vs chemotherapy (chemo) plus pembro. J Clin Oncol. 2026;44(suppl 17):LBA1000. doi:10.1200/JCO.2026.44.17_suppl.LBA1000