The battle for TROP2 in first-line triple-negative breast cancer has officially begun.
On Friday, Daiichi Sankyo and AstraZeneca announced that the FDA has approved their Datroway to treat patients with TNBC who are not candidates for PD-1/L1 inhibitors.
In a May 22 release, the companies were quick to point out that Datroway is currently the only TROP2-directed antibody-drug conjugate (ADC) that extends overall survival in this treatment setting compared to chemotherapy.
Datroway reduced the risk of death by 21% compared to chemotherapy in the phase 3 Tropion-Breast02 study. The drug extended median overall survival by five months to 23.7 months.
When data were presented at the 2025 European Society of Medical Oncology (ESMO) Congress in October, Gilead Sciences’ Ascent-03 trial of rival TROP2 ADC Trodelvy failed to meet statistical significance for overall survival in a similar first-line TNBC setting in patients not candidates for anti-PD-1/L1 therapy. Ascent-03 has enabled crossover to Trodelvy in the control arm as the disease progresses, and that is ongoing.
Datroway’s improvement in progression-free survival was 43%, which was numerically higher than Trodelvy’s 38% when compared between trials, but may be less reliable due to differences in underlying patient characteristics and trial design.
Gilead is likely to be far behind Daiichi and AZ. In addition to Ascent-03, Trodelvy also boasts positive results from Trodelvy’s Ascent-04 in combination with Merck & Co.’s Keytruda in first-line PD-L1-positive TNBC. Gilead will submit both indications to the FDA, with a decision expected in the second half of 2026. Researchers plan to share data on second-line treatment progress from both trials at the upcoming 2026 American Society of Clinical Oncology Annual Meeting.
Seven out of 10 patients with metastatic TNBC are not candidates for immunotherapy, Arlene Brothers, executive director of the Triple Negative Breast Cancer Foundation, said in a May 22 release from Arizona and Daiichi. “Today’s approval of Datroway means that for the first time, these patients will receive a new standard of care beyond traditional chemotherapy at the start of treatment.”
AZ and Daiichi are banking on Datroway’s unique overall survival win and sister physician Enherz’s halo effect in HER2-positive breast cancer for an advantage, while Gilead hopes its two positive trials in patients regardless of PD-L1 expression and physician knowledge of Trodelvy in second-line TNBC will drive physician preference.
Prior to Friday’s FDA approval, both Datroway and Trodelvy had been added to the National Comprehensive Cancer Network (NCCN) guidelines with the highest category 1 priority regimen recommendation for first-line TNBC.
With Gilead’s adoption, there is already some adoption of Trodelvy on the front lines, Chief Commercial Officer Joanna Mercier said during the company’s first quarter earnings call in early May.
Meanwhile, a third TROP2 ADC, Kelun-Biotech’s Merck-affiliated sacituzumab tilmothecan (sac-TMT), just reported positive Phase 3 results in first-line TNBC in China. The drug’s OpTiTROP-Breast03 study enrolled PD-L1-negative patients and patients with PD-L1-positive expression who relapsed after previous anti-PD-1/L1 therapy in the early stages.
To catch up with potentially differentiating Datroway and Trodelvy, Merck’s global Phase 3 TroFuse-011 trial is testing sac-TMT as monotherapy and in combination with Keytruda in PD-L1-negative TNBC.
Because patients in the control group will receive chemotherapy, the updated NCCN guidelines and Datroway’s approval may pose some difficulties in recruiting for that study in the United States.
Additionally, Datroway’s latest application was reviewed under Project Orbis, which facilitates simultaneous submission and review among international regulatory authorities. As part of that effort, Datroway’s case is also being evaluated in Australia, Canada, Singapore and Switzerland. Additional reviews are underway in the European Union, China and Japan.
