At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr Sara Tolaney (Dana-Farber Cancer Institute, Boston, MA, USA) presented pivotal results from the phase III ASCENT-04 trial. This study evaluated the efficacy of combining the antibody-drug conjugate sacituzumab govitecan with pembrolizumab versus standard chemotherapy plus pembrolizumab as first-line treatment in patients with PD-L1+ metastatic triple-negative breast cancer (TNBC). With an improvement in progression-free survival, the findings could point to a potential new standard of care for this aggressive breast cancer subtype. Dr. Tolaney discusses the rationale, study design and clinical implications of ASCENT-04’s results in this interview.
The late-breaking abstract, ‘Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1 positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study’ (LBA109) was presented at the American Society of Clinical Oncology on May 30 to June 3 2025 in Chicago, IL, USA.
Chapters
- Rationale (0:07.92)
- Methodology and trial design (1:00.85)
- Results (2:00.36)
- Conclusion (3:11.31)
Transcript
My name is Sarah Talaney. I’m a breast medical oncologist at Dana Farber Cancer Institute. This year at ASCO, we presented results of ASCENT-04, a randomized phase III study looking at sacituzumab govitecan plus pembrolizumab compared to chemotherapy plus pembrolizumab as first-line treatment for metastatic PD-L1+ triple negative breast cancer.
We know that the current standard of care for first line treatment of metastatic PDL-L1+ triple-negative breast cancer is chemotherapy with pembrolizumab, with the median PFS that’s been seen in prior trials being somewhere between 7-9 months. So there’s been a lot of interest to see if we could improve upon this, particularly since we know that antibody drug conjugates do better than chemotherapy, at least in pretreated triple-negative disease. And there does seem to be a lot of data to suggest that there could be synergistic activity between antibody drug conjugates and checkpoint inhibition. So ASCENT-04 really looked to investigate the efficacy of combining sacituzumab with pembrolizumab.
And so this trial enrolled patients who had never had any prior systemic therapy for their metastatic triple-negative disease, and tumors had to be centrally confirmed to be PD-L1+. So they had to have an assay that used a twenty two c three assay that had a combined positive score of ten or higher. And then patients were randomized one to one to get sacituzumab plus pembrolizumab or chemotherapy of physician’s choice plus pembrolizumab with choice of chemotherapy being paclitaxel or nab-paclitaxel or carboplatin with gemcitabine. And for those patients on the chemo-pembro arm, they were allowed to cross over to get sacituzumab monotherapy at time of progression on the chemo-pembro arm. And the sacituzumab was actually provided on the trial during the crossover phase of the study.
The primary endpoint was progression-free survival by blinded independent central review and demonstrated that sacituzumab plus pembrolizumab led to statistically significant, what I think is a clinically meaningful, improvement in progression-free survival, where we saw that the PFS for sacituzumab and pembrolizumab was 11.2 months compared to 7.8 months for chemotherapy and pembrolizumab with a hazard ratio of 0.65 with an absolute difference between the two arms of 3.4 months. So I think a very meaningful finding. The overall survival data is still very immature. It had 26% of survival events that were seen. And so survival was just looked at descriptively and had a trend towards benefit for sacituzumab and pembrolizumab with a hazard ratio of 0.89.
And of note, there were of the people who got chemo-pembro and then went on to get a subsequent line of therapy after progression, 80% of people who went on to get treated after chemo-pembro actually got sacituzumab. So I think that’s interesting to see such a high crossover rate.
So overall, I think these findings suggest that sacituzumab and pembrolizumab could be a new first-line standard of care, given the very impressive benefits.
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Disclosures: Sara Tolaney is a consultant for: Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics. She has received grant/research support from: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, SeaGen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharma. she is a member of the advisory board for: Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics. She has received honoraria/honorarium from: Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the American Society of Clinical Oncology (ASCO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Interviewer/Editor: Sophie Nickelson
Cite: #ASCO25: Sacituzumab combination shows promise in PD-L1+ TNBC in the ASCENT-04 study. touchONCOLOGY. June 12th, 2025.
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