Trodelvy gets one up on Datroway in triple-negative breast
Gilead’s TROP2 ADC prevails in Ascent-04, in first-line PD-L1-positive TNBC.
Gilead’s TROP2 ADC prevails in Ascent-04, in first-line PD-L1-positive TNBC.
Gilead’s TROP2-targeting ADC Trodelvy is facing a challenge from AstraZeneca and Daiichi’s similarly acting drug Datroway, but in triple-negative breast cancer it has retained its edge, at least for now. On Monday Gilead disclosed a topline win in Ascent-04, in first-line PD-L1-positive patients, namely those with 10% or higher expression.
Keytruda plus chemo has transformed this PD-L1-positive setting, but a Trodelvy/Keytruda combo produced a “statistically significant and clinically meaningful” progression-free survival benefit over this standard of care, Gilead said. Overall survival was immature, but there was an early trend towards improvement with Trodelvy plus Keytruda, the company added.
Full results will no doubt be pored over at a future medical meeting, but for now Trodelvy appears to have got one up on Datroway, whose similar study, Tropion-Breast05, isn’t due to yield data until next year. One difference is that the latter will test Datroway, with or without Imfinzi, versus Keytruda plus chemo.
PD-L1 negative
Both drugs are also being tested in first-line TNBC patients ineligible for checkpoint inhibitors for various reasons, including PD-L1 negativity, previous treatment with (neo)adjuvant Keytruda, or Keytruda ineligibility owing to comorbidities.
Here, however, readouts of the Ascent-03 trial of Trodelvy and the Tropion-Breast02 study of Datroway have been pushed back to the first half of this year, from the back end of 2024 previously.
Pivotal Trodelvy trials in TNBC
| Trial | Setting | Regimen | Timing | Analogous Datroway trial |
|---|---|---|---|---|
| Ascent-04 (Keynote-D19) | 1st-line TNBC (PD-L1+ve) | + Keytruda, vs Keytruda + chemo | Toplined positive Apr 2025 | Tropion-Breast05, data due 2026 |
| Ascent-03 | 1st-line TNBC (PD-L1-ve, or checkpoint inhibitor ineligible) | Monotherapy, vs chemo | Data due H1 2025 (from H2 2024) | Tropion-Breast02, data due H1 2025 (from H2 2024) |
| Ascent-05 | Adjuvant TNBC (following neoadjuvant therapy) | + Keytruda, vs Keytruda +/- chemo | Completes Jun 2027 | Tropion-Breast03, data due 2026 |
Source: OncologyPipeline & clinicaltrials.gov.
Merck and Kelun are also getting in on the act with their TROP2 contender sacituzumab tirumotecan, although so far the first-line TNBC trials have focused on the PD-L1-negative setting.
Adjuvant TNBC is shaping up to become another battleground, with Trodelvy in Ascent-05, Datroway in Tropion-Breast-03, and saci-T in the TroFuse-012 trial.
Trodelvy is already indicated in the US for late-line TNBC, as well as for relapsed ER-positive HER2-negative breast cancer; Datroway only has FDA approval for the latter.
While Trodelvy is seen by some as a TROP2 also-ran, it became a blockbuster in 2023. Still, Gilead has some way to go to justify the $21bn it paid for Immunomedics, the drug’s originator.
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