396MO - Anti-claudin 18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients (pts) with solid tumors and gastric/gastro-esophageal junction adenocarcinoma (G/GEJ AC): A phase I study

Background

CLDN18.2 is a promising target for solid tumors, particularly G/GEJ AC. IBI343 comprises anti-CLDN18.2 monoclonal antibody conjugated to exatecan (topoisomerase I inhibitor).

Methods

Eligible pts who failed or were intolerant to standard therapy were enrolled. Dose escalation evaluated IBI343 at 0.3/1/3/6/8/10 mg/kg Q3W. Selected dose levels were expanded in G/GEJ AC pts with positive CLDN18.2 expression, defined as ≥1% tumor cells with membranous staining (1+/2+/3+) by IHC. Endpoints were safety and efficacy per RECIST v1.1.

Results

As of Jan 15, 2024, 159 pts in China and Australia were enrolled with 79 pts at 6 mg/kg and 51 pts at 8 mg/kg. DLTs were observed in 2 of 6 pts at 10 mg/kg. TEAEs occurred in 149 pts (93.7%) with ≥G3 TEAEs in 79 pts (49.7%). Most common TEAEs were anemia (54.7%), white blood cell count decreased (47.8%), and neutrophil count decreased (46.4%). Gastrointestinal toxicities ≥G3 were rarely reported including vomiting (1.9%), nausea (1.3%) and decreased appetite (1.3%). Hypoalbuminemia occurred in 24.5% pts and no pts had ≥G3 event. TRAEs led to treatment discontinuation in 2 (1.3%) pts. No TRAE led to death. As of Mar 29, 2024, 99 pts with any CLDN18.2 expression G/GEJ AC were efficacy evaluable (prior treatments ≥2L: 73.7%, prior immunotherapy: 82.0%). Overall ORR was 32.3% (95% CI: 23.3-42.5) and DCR was 75.8% (95% CI: 66.1-83.8). In pts with CLDN18.2 (2+/3+ ≥40%), ORR and DCR at 6 mg/kg (n=48) were 37.5% (95% CI: 24.0-52.6) and 89.6% (95% CI: 77.3-96.5), at 8 mg/kg (n=29) were 44.8% (95% CI: 26.4-64.3) and 82.8% (95% CI: 64.2-94.2). Median PFS was 5.6 months (95% CI: 4.2-7.3) at 6 mg/kg (median follow-up:7.2 months) and 5.5 months (95% CI: 4.2-NC) at 8mg/kg (median follow-up: 4.6 months). In pts with CLDN18.2 (2+/3+ ≥75%), ORR and DCR at 6 mg/kg (n=30) were 46.7% (95% CI: 28.2-65.7) and 93.3% (95% CI: 77.9-99.2), at 8 mg/kg (n=17) were 52.9% (95% CI: 27.8-77.0) and 88.2% (95% CI: 63.6-98.5). Median PFS was 6.8 months (95% CI: 4.2-NC) at 6 mg/kg (median follow-up: 7.2 months) and 5.5 months (95% CI: 4.2-NC) at 8 mg/kg (median follow-up: 4.6 months).

Conclusions

IBI343 was well tolerated in all pts with encouraging efficacy in CLDN18.2-postive G/GEJ AC.

Clinical trial identification

NCT05458219.

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

H. Zhou: Other, Personal and Institutional, Full or part-time Employment: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.