Efficacy of IBI343 in CLDN18.2-Positive G/GEJ AC

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

Jia Jenny Liu and the team aimed to assess the efficacy and safety of IBI343 in patients (pts) with solid tumors, focusing on those with CLDN18.2-positive G/GEJ AC.

Researchers performed an inclusive analysis of eligible pts who had failed or were intolerant to standard therapy. Dose escalation of IBI343 was conducted at 0.3, 1, 3, 6, 8, and 10 mg/kg every 3 weeks. Selected dose levels were expanded in pts with G/GEJ AC showing ≥1% tumor cells with membranous CLDN18.2 expression (1+/2+/3+) by IHC. Safety and efficacy endpoints were assessed.

About 159 pts from China and Australia were enrolled as of January 15, 2024, with 79 pts receiving 6 mg/kg and 51 pts receiving 8 mg/kg of IBI343. Dose-limiting toxicities (DLTs) occurred in 2 out of 6 pts at 10 mg/kg. Treatment-emergent adverse events (TEAEs) affected 149 pts (93.7%), with severe (≥Grade (G) 3) TEAEs in 79 pts (49.7%).

The most common TEAEs included anemia (54.7%), decreased white blood cell count (47.8%), and decreased neutrophil count (46.4%). Severe gastrointestinal toxicities were infrequent, with vomiting, nausea, and decreased appetite each reported in less than 2% of pts. Hypoalbuminemia affected 24.5% of pts without severe cases. TEAEs led to treatment discontinuation in 1.3% of pts, with no treatment-related deaths reported.

As of March 29, 2024, efficacy was evaluated in 99 pts with any CLDN18.2 expression in G/GEJ AC, of whom 73.7% had received at least 2 prior lines of treatment and 82.0% had undergone prior immunotherapy. The overall objective response rate (ORR) was 32.3% (95% CI: 23.3-42.5), and the disease control rate (DCR) was 75.8% (95% CI: 66.1-83.8). Among pts with CLDN18.2 (2+/3+ ≥40%), ORR and DCR at 6 mg/kg were 37.5% (95% CI: 24.0-52.6) and 89.6% (95% CI: 77.3-96.5), respectively, and at 8 mg/kg (n=29) were 44.8% (95% CI: 26.4-64.3) and 82.8% (95% CI: 64.2-94.2), respectively.

The median progression-free survival (PFS) was 5.6 months (95% CI: 4.2-7.3) at 6 mg/kg and 5.5 months (95% CI: 4.2-NC) at 8 mg/kg. In pts with CLDN18.2 (2+/3+ ≥75%), ORR and DCR at 6 mg/kg were 46.7% (95% CI: 28.2-65.7) and 93.3% (95% CI: 77.9-99.2), respectively, and at 8 mg/kg were 52.9% (95% CI: 27.8-77.0) and 88.2% (95% CI: 63.6-98.5), respectively. Median PFS was 6.8 months (95% CI: 4.2-NC) at 6 mg/kg and 5.5 months (95% CI: 4.2-NC) at 8 mg/kg.

The study concluded that IBI343 demonstrated favorable tolerability in all pts and showed promising efficacy in CLDN18.2-positive G/GEJ AC.

The trial was sponsored by the Innovent Biologics (Suzhou) Co. Ltd.

Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/34

Clinical Trial: https://clinicaltrials.gov/study/NCT05458219

Jia Jenny Liu, Xianjun Yu, Jian Zhang, et al. (2024). “396MO – Anti-claudin 18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in pts (pts) with solid tumors and gastric/gastro-esophageal junction adenocarcinoma (G/GEJ AC): A phase I study.” Presented at ESMO-GI 2024 (Abstract 396MO).