132MO - Anti-claudin18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC): Updated results from a phase I study

Background

CLDN18.2 is a potential target for solid tumors including PDAC. IBI343, consisting of anti-CLDN18.2 monoclonal antibody and topoisomerase I inhibitor exatecan, has shown favorable safety profile with encouraging efficacy in CLDN18.2-positive PDAC (2024 ASCO Annual Meeting, abstract 3037). Herein, we report updated results of IBI343 in PDAC.

Methods

Eligible pts with advanced PDAC and positive CLDN18.2 expression (defined as ≥ 60% intensity of 1+/2+/3+ staining cells by IHC) who failed or were intolerant to standard treatment were enrolled. IBI343 was intravenously administered at 6 mg/kg Q3W. Endpoints were safety, investigator-assessed ORR, DCR, DoR, PFS per RECIST v1.1, and OS.

Results

As of July 6, 2024, 43 pts were enrolled from China and Australia (median age: 60.0 years, males: 55.8%, prior treatments ≥2L: 53.5%, prior irinotecan therapy: 46.5%, prior immunotherapy: 22.0%). TEAEs occurred in 42 (97.7%) pts including ≥G3 TEAEs in 19 (44.2%) pts. Most common TEAEs were anemia (48.8%, 14.0% ≥G3), neutrophil count decreased (48.8%, 11.6% ≥G3), nausea (46.5%, none ≥G3), white blood cell count decreased (44.2%, 9.3% ≥G3), decreased appetite (44.2%, 4.7% ≥G3) and hypoalbuminemia (37.2%, none ≥G3). No other gastrointestinal toxicities ≥G3 was observed, expect for intestinal obstruction in 2 pts (4.7%). TEAEs led to treatment discontinuation in 3 (7.0%) pts. No TEAE led to death. Safety profile of IBI343 in PDAC was comparable to previous reports. No new safety signal was observed. Efficacy was evaluable in 41 pts with ORR of 24.4% (95% CI: 12.4-40.3), including 3 pts pending confirmation, and DCR of 80.5% (95% CI: 65.1-91.2). In 7 pts with confirmed PR, median DoR was 7.7 months (95% CI: 4.0-NC) with events occurred in 2 (28.6%) pts. In all pts, median PFS was 5.3 months (95% CI: 2.8-10.5) with a median follow-up of 5.4 months.

Conclusions

IBI343 was well tolerated and continued to show favorable safety profiles and encouraging efficacy in CLDN18.2-positive PDAC. The trial continues to enroll and more data will be presented at the meeting.

Clinical trial identification

NCT05458219.

Editorial acknowledgement

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

X. Yu, X. Zhao, M. Chen: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd. All other authors have declared no conflicts of interest.