European journal of cancer (Oxford, England : 1990) · 2026
A phase I, first-in-human dose-escalation and triple-negative breast cancer dose-expansion study of a TROP2-ADC F0024 (FDA018).
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Du Yiqun, Meng Yanchun, Liu Xiaojun, Wang Jingfen, Wang Ying, Wu Fan, Chen Yu, Chen Lilin, Qing Lihua, Sun Wenyi, Liu Kezhen, Zhang Jian
Аннотация
BACKGROUND: This first-in-human, phase I study (NCT05174637) assessed F0024 (FDA018), a TROP2-directed ADC, in advanced solid tumors, including a dose-expansion cohort in triple-negative breast cancer (TNBC).
METHODS: Participants were intravenously administered F0024 (2.5-15 mg/kg) in the dose-escalation phase to determine the safety and tolerability. Dose-expansion cohorts of patients with heavily pretreated TNBC received doses of 10 or 12 mg/kg to further assess the efficacy and safety.
RESULTS: 67 participants were enrolled (26 in dose-escalation and 41 in TNBC expansion). Two dose-limiting toxicities occurred. Dose escalation was halted at 15 mg/kg due to cumulative toxicity concerns. Across escalation cohorts, grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 56.0% and increased with dose. Notable antitumor activity was observed from 5 mg/kg, with an objective response rate (ORR) of 66.7% in the 10 mg/kg group. In the TNBC population, 10 mg/kg achieved an ORR of 37.9% and a median PFS of 10.5 months; 12 mg/kg showed an ORR of 23.5% and a PFS of 4.3 months. Grade ≥ 3 TRAEs occurred in 57.7% of the pooled TNBC population; serious TRAEs were reported in 9.6%.
CONCLUSION: F0024 demonstrated promising antitumor activity in TNBC, with manageable but frequent hematologic toxicity and dose modifications. The recommended phase II dose (RP2D) is 10 mg/kg.
METHODS: Participants were intravenously administered F0024 (2.5-15 mg/kg) in the dose-escalation phase to determine the safety and tolerability. Dose-expansion cohorts of patients with heavily pretreated TNBC received doses of 10 or 12 mg/kg to further assess the efficacy and safety.
RESULTS: 67 participants were enrolled (26 in dose-escalation and 41 in TNBC expansion). Two dose-limiting toxicities occurred. Dose escalation was halted at 15 mg/kg due to cumulative toxicity concerns. Across escalation cohorts, grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 56.0% and increased with dose. Notable antitumor activity was observed from 5 mg/kg, with an objective response rate (ORR) of 66.7% in the 10 mg/kg group. In the TNBC population, 10 mg/kg achieved an ORR of 37.9% and a median PFS of 10.5 months; 12 mg/kg showed an ORR of 23.5% and a PFS of 4.3 months. Grade ≥ 3 TRAEs occurred in 57.7% of the pooled TNBC population; serious TRAEs were reported in 9.6%.
CONCLUSION: F0024 demonstrated promising antitumor activity in TNBC, with manageable but frequent hematologic toxicity and dose modifications. The recommended phase II dose (RP2D) is 10 mg/kg.