345MO IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with advanced solid tumors and breast cancer (BC): Results from a phase I study.

Abstract

Background: IBI354 is an ADC comprising trastuzumab (anti-HER2 antibody) conjugated to a topoisomerase I inhibitor. We report a global multicenter, phase I study of IBI354 in pts with advanced solid tumors. Method(s): Eligible pts who failed or were intolerant of standard treatment were enrolled. HER2 alterations were assessed by IHC (1+/2+/3+), FISH, or NGS. IBI354 was administered at 0.8-15 mg/kg Q3W or Q2W. Dose levels >= 6 mg/kg were selected for dose expansion. Primary endpoint was safety. Secondary endpoints were ORR, DCR, DoR, and PFS per RECIST v1.1. Result(s): As of Mar 22, 2024, 318 pts in China and Australia were enrolled (females: 89.9 %, median age: 56.0 yrs, ECOG PS 1: 73.0%, prior treatment regimens >=2: 85.8%). Median treatment duration was 14.2 weeks (range: 3.1-37.3) with 215 (67.6%) pts still on treatment. No dose-limiting toxicity occurred across all dose levels explored. Treatment-related adverse events (TRAEs) occurred in 257 (80.8%) pts. Grade >=3 TRAEs occurred in 16.7% of total pts (commonly [>= 1%] being neutropenia [5.3%], leukopenia [3.5%], and anemia [2.5%]) and in 16.0% of pts in 12 mg/kg Q3W cohort. Serious TRAEs occurred in 11 (4.1%) pts. One (0.3%) pt required dose reduction and 1 (0.3%) required treatment discontinuation for TRAEs. No TRAE led to death. Interstitial lung disease (grade 1) occurred in 1 (0.3%) pt. As of Apr 25, 2024, for HER2-positive (HER22+/FISH+ or 3+) BC pts with at least one tumor assessment (n=44, median lines of prior treatments: 4), ORR was 61.4% (95% CI: 45.5-75.6) and DCR was 88.6% (95%CI: 75.4-96.2). ORR and DCR for each dose level were 57.1% (95% CI: 28.9-82.3) and 85.7% (95% CI: 57.2-98.2) for 6 mg/kg Q3W (n=14), 53.3% (95% CI: 26.6-78.7) and 86.7% (95% CI: 59.5-98.3) for 9 mg/kg Q3W (n=15), and 73.3% (95% CI: 44.9-92.2) and 93.3% (95% CI: 68.1-99.8) for 12 mg/kg Q3W (n=15). For the HER2-low (HER21+ or 2+/FISH-) BC pts with at least one tumor assessment at 12 mg/kg Q3W (n=26, median lines of prior treatments: 4), ORR was 53.8% (95% CI: 33.4-73.4) and DCR was 88.5% (95% CI: 69.8-97.6). DoR and PFS were immature. Conclusion(s): IBI354 was well tolerated, including at higher doses up to 12 mg/kg. Promising efficacy was observed in both HER2-positive and HER2-low BC. Clinical trial identification: NCT05636215. Legal entity responsible for the study: Innovent Biologics (Suzhou) Co., Ltd. Funding(s): Innovent Biologics (Suzhou) Co., Ltd. Disclosure: H. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.Copyright © 2024