IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with HER2-positive breast cancer (BC) and other solid tumors: Updates from a phase 1 study.

Abstract

1029Background: HER2 has been established as an important therapeutic target for BC. IBI354 consists of trastuzumab (anti-HER2 antibody) conjugated to a camptothecin derivative. In a global, multicenter, phase 1 study, IBI354 was well tolerated and showed promising efficacy in BC and other solid tumors (2024 ESMO 345MO/720MO/576P). Here, we report updated safety and efficacy of IBI354. Method(s): Eligible pts with advanced solid tumors who had failed or were intolerant to standard treatment were enrolled. Positive HER2 was defined as immunohistochemistry (IHC) 2+/in situ hybridization (ISH)+ or IHC 3+. IBI354 was administered intravenously at 6-15 mg/kg Q3W or Q2W. Primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progress-free survival (PFS) assessed by investigators per RECIST v1.1 and overall survival (OS). Result(s): As of Nov 12, 2024, a total of 368 pts with solid tumors were enrolled in China and Australia (females: 89.4%, median age: 56.0 years [range: 27-82], ECOG PS 1: 75.0%). Median follow-up time was 11.3 months (range: 5-19). Median treatment duration was 25.0 weeks (range: 3.1-63.3) and 124 (33.7%) pts remain on treatment. Treatment-related adverse events (TRAEs) occurred in 331 (89.9%) pts while >=grade 3 (G3) TRAEs occurred in 93 (25.3%) pts. Most common TRAEs included white blood cell count decreased (48.6%, with 7.1% >=G3), anemia (46.7%, with 4.9% >=G3), nausea (46.2%, with 0.8% >=G3) and neutrophil count decreased (38.3%, with 9.8% >=G3). Interstitial lung disease occurred in 8 (2.2%) pts (5 treatment-related and 3 treatment-unrelated, all G1-2). TRAEs led to dose reduction in 5 (1.4%) pts and treatment discontinuation in 4 (1.1%) pts. No TRAE led to death. Efficacy was evaluable in 88 pts with HER2-positive BC (stage IV: 97.7%; prior systemic therapy regimens>=5: 65.9%; IHC 2+/ISH+: 19.3%, IHC 3+: 80.7%). The overall confirmed ORR was 58.0% (95% CI: 47.0-68.4) and DCR was 90.9% (95% CI: 82.9-96.0). Among 51 pts with confirmed responses, median DoR was not reached (events rate: 19.6%) and 12-month DoR rate of 71.8% (95% CI: 52.9-84.2). Median PFS was not reached with events rate of 37.5%. Median OS was not reached with events rate of 5.7% and 9-month OS rate of 96.2% (95% CI: 88.7-98.8). Conclusion(s): IBI354 continues to demonstrate favorable safety profiles with no new safety signals. Encouraging efficacy was observed in HER2-positive BC. Clinical trial information: NCT05636215.Copyright © 2025 by American Society of Clinical Oncology