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Showed that pairing an ADC with immunotherapy beats chemotherapy plus immunotherapy in first-line PD-L1-positive TNBC.
ASCENT-04, also KEYNOTE-D19, trial NCT05382286 sponsored by Gilead and Merck and reported at ESMO 2025, showed that pairing the antibody-drug conjugate sacituzumab govitecan with pembrolizumab beats chemotherapy plus pembrolizumab in first-line PD-L1-positive metastatic triple-negative breast cancer. It randomised 443 patients with a combined positive score of ten or more, met its primary progression-free survival endpoint by blinded review, showed improved time to second progression at ASCO 2026 with overall survival immature, and was approved in 2026, establishing ADC plus checkpoint inhibitor as the new first-line standard for PD-L1-positive disease. OnCo links it to triple-negative breast cancer, sacituzumab govitecan, pembrolizumab, the ADC plus checkpoint inhibitor pairing and four roadmaps. Whether the survival benefit follows is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
443 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (BICR)primary | Sacituzumab govitecan + pembrolizumab | 221 | 11.2 months | 0.65 (0.51 to 0.84) | 0.0009 | link |
| Chemotherapy + pembrolizumab | 222 | 7.8 months | ||||
| Objective response rate | Sacituzumab govitecan + pembrolizumab | - | 60% | - | - | link |
| Chemotherapy + pembrolizumab | - | 53% | ||||
| Overall survival | Sacituzumab govitecan + pembrolizumab | - | Immature; PFS2 favoured the ADC arm in the ASCO 2026 update. | - | - | link |
| Chemotherapy + pembrolizumab | - | - |
NCCN is the source of the category grades on the triple-negative breast cancer page and the first major guideline to place an antibody-drug conjugate first line for the disease.
This is the paper Europe PMC returns for registry id NCT05382286 with the most citations, so it is the natural first reading for anyone following the ASCENT-04 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
Shares Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology, TROP2 PET to choose and sequence TROP2 ADCs, ASCENT, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line.
Shares ADC + checkpoint inhibitor, Trials that include, and report, brain metastases in triple-negative breast cancer, KEYNOTE-355, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line.
Shares Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology, TROP2 PET to choose and sequence TROP2 ADCs, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET.
Shares Trials that include, and report, brain metastases in triple-negative breast cancer, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Metastatic triple-negative breast cancer.
Shares ASCENT, ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer, TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs.
Shares TROP2 PET to choose and sequence TROP2 ADCs, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs.
Shares Gilead Sciences (incl. Kite), Sacituzumab govitecan, Metastatic triple-negative breast cancer, Topoisomerase-I inhibitors (and ADC payloads).
Shares KEYNOTE-355, ASCENT, Metastatic triple-negative breast cancer, Merck & Co. (MSD).