A phase I, first-in-human dose-escalation and triple-negative breast cancer dose-expansion study of a TROP2-ADC F0024 (FDA018).
Yiqun Du, Yanchun Meng, Xiaojun Liu et al.
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In 30 seconds
This multicenter, first-in-human phase I dose-escalation and dose-expansion study evaluated the TROP2-directed antibody–drug conjugate F0024 (FDA018) in advanced solid tumors, including heavily pretreated triple-negative breast cancer (TNBC). Among 67 participants, dose escalation stopped at 15 mg/kg because of cumulative toxicity concerns. In the TNBC expansion, the 10 mg/kg group had an objective response rate (ORR) of 37.9% and median progression-free survival (PFS) of 10.5 months, compared with an ORR of 23.5% and PFS of 4.3 months at 12 mg/kg. The investigators selected 10 mg/kg as the recommended phase II dose.
Key findings
- In TNBC, the 10 mg/kg group had an ORR of 37.9% and median PFS of 10.5 months.
- At 12 mg/kg in TNBC, ORR was 23.5% and PFS was 4.3 months.
- Grade ≥ 3 treatment-related adverse events occurred in 57.7% of the pooled TNBC population; serious treatment-related adverse events occurred in 9.6%.
- Across dose-escalation cohorts, grade ≥ 3 treatment-related adverse events occurred in 56.0% and increased with dose; escalation stopped at 15 mg/kg over cumulative toxicity concerns.
Why it matters
The study provides early clinical evidence of antitumor activity for a TROP2-directed ADC in heavily pretreated TNBC, while also documenting frequent high-grade toxicity. The differing outcomes reported at 10 and 12 mg/kg, alongside dose-related toxicity concerns, underscore the importance of dose selection and further evaluation before the treatment’s role can be established.
What to keep in mind
This was an early-phase study with small dose-specific TNBC cohorts; the abstract does not report a comparator, limiting conclusions about comparative efficacy.