Safety and efficacy of the anti-TROP2 antibody-drug conjugate (ADC) IBI130 in patients (pts) with advanced triple-negative breast cancer (TNBC) and other solid tumors: Results from the phase 1 study.

Background: TROP2 is a promising therapeutic target in various solid tumors. IBI130 is composed of an anti-TROP2 antibody conjugated to the camptothecin derivative NT1. Herein, we report the multi-regional, first-in-human, phase 1 study of IBI130. Methods: Eligible pts with unresectable locally advanced or metastatic solid tumors who failed or intolerant to standard treatment were enrolled. The study included dose escalation and dose expansion. IBI130 was intravenously administered at 1/2/4/6/8/10/12 mg/kg Q3W during dose escalation, which was guided by modified continuous reassessment method (mCRM) according to Bayesian logistic regression model (BLRM) and escalation with overdose control (EWOC) principle. Primary endpoint was safety. Secondary endpoint was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS). Results: As of Dec 15, 2024, 71 pts were enrolled from China and Australia (median age: 60 years [range: 30-81], female: 85.9%, Caucasian: 16.9%, ECOG PS 1: 48.6%; prior lines of anticancer treatment≥2: 63.8%). Median follow-up of the study was 4.6 months (range: 0.8-9.7). No dose-limiting toxicity (DLT) was observed across all dose levels during dose escalation (n = 18). Median treatment duration was 18 weeks (range: 3-45) with 40 (56.3%) pts still on treatment. Treatment-emergent adverse events (TEAEs) occurred in 68 (95.8%, with 90.1% treatment-related adverse events [TRAEs]) pts including grade 3 (G3) events in 17 (23.9%, with 15.5% TRAEs) pts. No grade 4-5 events occurred. Common TEAEs (≥30%) were stomatitis (52.1%, with 9.9% G3), nausea (31.0%, with 2.8% G3) and rash (31.0%, with 1.4% G3). Interstitial lung disease occurred in 1 pt (1.4%, G1). Only 1 pt (1.4%) had G3 lymphocyte count decreased. Other ≥G3 hematological toxicities were not observed. TRAEs led to dose reduction in 5 (7.0%) pts and treatment discontinuation in 1 (1.4%) pts. Efficacy of IBI130 was evaluable in 30 pts with TNBC treated at 4/6/8/10 mg/kg (all stage IV, and 96.7% had failed or were intolerant to taxanes). The overall ORR was 50.0% (95% CI: 31.3-68.7) and DCR was 83.3% (95% CI: 65.3-94.4). As for different dose levels, ORR and DCR were 40.0% (95% CI: 5.3-85.3) and 60.0% (95% CI: 14.7-94.7) for 4 mg/kg (n = 5), 40.0% (95% CI: 5.3-85.3) and 80.0% (95% CI: 28.4-99.5) for 6 mg/kg (n = 5), 50.0% (95% CI: 18.7-81.3) and 100% (95% CI: 69.2-100.0) for 8 mg/kg (n = 10), 60.0% (95% CI: 26.2-87.8) and 80.0% (95% CI: 44.4-97.5) for 10 mg/kg (n = 10). DoR and PFS data were not mature as of the cutoff date. Conclusions: IBI130 was well tolerated featured by superiority of hematological safety, and encouraging efficacy of IBI130 was observed in advanced TNBC, supporting its potential as a best-in-class TROP2 ADC. Clinical trial information: NCT05923008.