Safety and efficacy of IBI354 (anti-HER2 ADC) in patients (pts) with advanced gastrointestinal (GI) cancers: Results from a phase I study.

Abstract

Background: IBI354, an antibody-drug conjugate (ADC), composed of trastuzumab (anti-HER2 antibody) conjugated to a topoisomerase I inhibitor. We report safety and efficacy of IBI354 in pts with advanced GI cancers in a multicenter, phase 1 study. Method(s): Eligible pts with advanced/unresectable or metastatic colorectal cancer (CRC), biliary tract cancers (BTC), gastric and gastroesophageal junction carcinoma (G/GEJC) and other GI cancers who failed or were intolerant of standard treatment were enrolled. IBI354 was administered at 0.8-15 mg/kg Q3W or Q2W. Primary endpoint was safety. Secondary endpoints were ORR, DCR, DoR, and PFS assessed per RECIST v1.1. In this report, safety and efficacy were evaluated in HER2 IHC 3+ or ISH/FISH+ pts with GI cancers at dose levels of >=6mg/kg Q3W or Q2W. Result(s): As of Mar 22, 2024, 34 pts were enrolled (male: 61.8%, median age: 59.0 yrs, ECOG PS 1: 91.2%, stage IV: 100%, prior treatment regimens >=2: 76.5%, CRC: 73.5%). Median treatment duration was 21.1 weeks (range: 6.1-37.3). Treatment-related adverse events (TRAEs) occurred in 30 (88.2%) pts and grade >=3 TRAEs in 6 (17.6%) pts. Common TRAEs (>= 20%) were nausea (55.9%), anemia (32.4%), neutrophil count decreased (29.4%), and white blood cell count decreased (26.5%). No interstitial lung disease (ILD) was observed. Serious TRAEs were not observed. No TRAEs led to dose reduction, treatment discontinuation, or death. The safety profiles of IBI354 in GI cancers were comparable with the whole study cohort. As of Apr 25, 2024, in 34 pts with at least one tumor assessment, ORR was 55.9% (95% CI: 37.9-72.8) and DCR was 91.2% (95% CI: 76.3-98.1). A total of 19 pts had partial response including 3 of 4 pts with HER2 IHC 2+/FISH+ or ISH+ (1 G/GEJC, 1 BTC and 1 CRC), 16 of 30 pts with HER2 IHC 3+ (13 CRC, 2 BTC and 1 G/GEJC). DoR and PFS were immature. Conclusion(s): IBI354 was well tolerated and showed encouraging efficacy in pts with advanced GI cancers. Clinical development of IBI354 in these tumor types are ongoing. More data will be updated at the meeting. Clinical trial identification: NCT05636215. Legal entity responsible for the study: Innovent Biologics (Suzhou) Co., Ltd. Funding(s): Innovent Biologics (Suzhou) Co., Ltd. Disclosure: Y. Luo, Y. Zhang, H. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd. All other authors have declared no conflicts of interest.Copyright © 2024