Outstanding safety and efficacy data of IMC002, an autologous CLDN18.2-targeting CAR-T, in CLDN18.2+ advanced solid tumors.

e16012 Background: Claudin 18.2 (CLDN18.2) is a promising therapeutic target for advanced solid tumors with CLDN18.2 expression. IMC002 is an autologous CLDN18.2-targeting CAR-T cell directed by a CLDN18.2-specific VHH, the specificity of which was confirmed by a membrane proteome array assay. Preclinical studies showed that IMC002 exhibited high tumor specificity, anti-tumor efficacy, and excellent safety profile in both cell and animal models. Methods: This is an open label first in human Phase 1 dose escalation study to evaluate the safety and efficacy of IMC002 in advanced solid tumors with CLDN18.2 expression which is defined as CLDN18.2 expression of ≥1+ membrane staining intensity in ≥10% tumor cells. Accelerated titration followed by Bayesian optimal interval design was adopted with a total of 4 dose levels planned at 1, 3, 5 and 7 million (mil) CAR-T cells/kg respectively. All patients (pts) were given a single dose of IMC002 infusion after lymphodepletion chemotherapy. Dose limiting toxicity (DLT) was evaluated during the 28-day period after IMC002 infusion. Safety, anti-tumor activity, pharmacokinetics and pharmacodynamics were explored in this study. Here, we present preliminary safety and efficacy data for the pts dosed with up to 3 mil CAR-T cells/kg. Results: As of January 17, 2024, 3 advanced unresectable gastric cancer pts received IMC002 infusion, 1 patient at 1 mil CAR-T cells/kg and 2 pts at 3 mil CAR-T cells/kg. No DLT or SAE was reported. Manageable CRS (grade 1) was reported in all 3 pts. Other adverse events related to cell therapy included grade 1-2 lipase increase (3/3), diarrhea (1/3), pruritis (1/3) and γ-GGT increase (1/3). All adverse events recovered quickly. Preliminary efficacy data showed that best overall response of the 3 pts was all stable disease as evaluated by RECIST 1.1. The two pts at the dose level of 3 mil CAR-T cells/kg underwent successful radical surgery at week (W) 11 and 44 after IMC002 infusion respectively. Pathological complete response (pCR) was achieved in the patient with surgery at W44. Distinct CAR-T cell expansion in peripheral blood was observed in all 3 pts, with the peak number of CAR+ cells reaching on day 7-11 in the peripheral blood after the infusion. Moreover, CAR-T cell infiltration was detected in the W11 and W44 surgical samples. Significant elevations of serum levels of IFN-γ, IL-10, IP-10, IL-2 and IL-6 were observed in the 3 pts. The trial is ongoing. Conclusions: IMC002 showed a favorable safety profile, encouraging anti-tumor activities with observed pCR and persistent expansion in the tumor tissue at the low dosage levels in pts with advanced CLDN18.2+ gastric cancer. In addition, our trial has successfully provided a surgical treatment opportunity after CAR-T therapy downstaging of unresectable gastric cancers. Clinical trial information: NCT05472857 .