Clinical trialPhase 3Breast cancer

Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer

N Engl J Med · 2026443 patients (221 sacituzumab govitecan + pembrolizumab, 222 chemotherapy + pembrolizumab)

Tolaney SM, de Azambuja E, Kalinsky K, et al. N Engl J Med. 2026. 394:354-366

Study type: Clinical trial
Study name: ASCENT-04/KEYNOTE-D19
Phase: Phase 3
Design: Randomised, open-label, international trial; 1:1 randomisation
Sample size: 443 patients (221 sacituzumab govitecan + pembrolizumab, 222 chemotherapy + pembrolizumab)
Source: N Engl J Med · 2026
Trial registration: NCT05382286

In plain words

In metastatic triple-negative breast cancer that carries the PD-L1 protein, first treatment is usually chemotherapy combined with the immunotherapy drug pembrolizumab (Keytruda). In ASCENT-04, replacing chemotherapy with sacituzumab govitecan (Trodelvy) alongside pembrolizumab extended the median time the disease was kept under control from 7.8 to 11.2 months, and responses lasted longer. Serious side effects were similar in both groups, but fewer patients had to stop treatment because of side effects. It is not yet known whether this treatment helps people live longer overall.

Key results

11.2 vs 7.8 months

Median progression-free survival

HR 0.65 (95% CI, 0.51 to 0.84); two-sided P<0.001

60% vs 53%

Objective response

16.5 vs 9.2 months

Median duration of response

12% vs 31%

Discontinuation due to adverse events

Overall survival data were still immature

Drugs in this study:Carboplatin (Paraplatin)Gemcitabine (Gemzar)Paclitaxel (Taxol)Pembrolizumab (Keytruda)

Dose and schedule cards

Sacituzumab govitecan + pembrolizumab (ASCENT-04/KEYNOTE-D19)

Untreated advanced TNBC with PD-L1 CPS ≥10; if treated at an early stage, at least 6 months between the end of curative treatment and recurrenceCycle length: Every 21 daysOn the page “Breast cancer” · Advanced triple-negative disease or disease with a germline BRCA mutation

Untreated advanced TNBC with PD-L1 CPS ≥10; if treated at an early stage, at least 6 months between the end of curative treatment and recurrence

Drug	Dose	Route	Schedule
Sacituzumab govitecan	10 mg/kg (do not exceed)	IV	Days 1 and 8
Pembrolizumab	200 mg	IV	Day 1

Cycle length: Every 21 days
Duration: Sacituzumab until progression or toxicity; pembrolizumab for about 24 months

Premedication: an antipyretic and H1 and H2 antihistamines before the infusion (plus a corticosteroid if there is a history of infusion reactions); two-‎ or three-drug antiemetic prophylaxis (dexamethasone with a 5-HT3 or NK1 antagonist). Neutropenia: primary G-CSF prophylaxis from the first cycle in patients at high risk of febrile neutropenia; give on day 1 with an ANC of at least 1500 and on day 8 with an ANC of at least 1000. UGT1A1*28 homozygotes are at higher risk of neutropenia and anaemia. Dose reduction: 7.5 and then 5 mg/kg. Do not substitute with irinotecan-containing drugs.

On the page “Breast cancer” · Advanced triple-negative disease or disease with a germline BRCA mutation

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Sacituzumab govitecan + pembrolizumab

Sacituzumab govitecan 10 mg/kg IV on days 1 and 8 of each 21-day cycle, with pembrolizumab 200 mg IV on day 1 of each 21-day cycle (pembrolizumab for a maximum of 35 cycles).

2Chemotherapy + pembrolizumab (control arm)

Pembrolizumab 200 mg on day 1 of each 21-day cycle (maximum 35 cycles) with one of the following regimens of physician's choice: paclitaxel 90 mg/m² on days 1, 8 and 15 every 28 days; nab-paclitaxel 100 mg/m² on days 1, 8 and 15 every 28 days; or gemcitabine 1000 mg/m² + carboplatin AUC 2 on days 1 and 8 every 21 days. Crossover to single-agent sacituzumab govitecan after progression was allowed.

Source of the regimen details: FDA label for Trodelvy (TRODELVY, version 2026-06, sections 2 and 14); ClinicalTrials.gov NCT05382286.

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with previously untreated (no prior systemic therapy for advanced disease), PD-L1-positive (CPS ≥ 10 by the 22C3 assay) unresectable locally advanced or metastatic triple-negative breast cancer. Per the FDA label, at least 6 months must have elapsed between completion of treatment with curative intent and recurrence; prior PD-1/PD-L1 inhibitor use in the early-stage setting was allowed.

Endpoints

Primary endpoint: progression-free survival (by blinded independent central review).

Secondary endpoints: overall survival, objective response (complete or partial response) and duration of response (by blinded independent central review), and safety.

Safety and side effects

Grade 3 or higher adverse events occurred in 71% of the sacituzumab govitecan + pembrolizumab group and 70% of the chemotherapy + pembrolizumab group. Discontinuation due to adverse events was 12% and 31%, respectively. Fatal adverse events occurred in 3% of patients in each group.

Clinical significance and place in guidelines

On 24 June 2026 the FDA approved sacituzumab govitecan with pembrolizumab for the first-line treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer expressing PD-L1 (CPS ≥ 10). In Europe, the CHMP of the European Medicines Agency (EMA) issued a positive opinion for this combination in July 2026.

Limitations

The trial was open-label. Overall survival data were immature at the time of reporting, and crossover to sacituzumab govitecan after progression was allowed in the control arm, which may complicate interpretation of overall survival. The results apply only to PD-L1-positive (CPS ≥ 10) patients.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.