737MO - EpCAM-targeted CAR-T cell therapy in patients with advanced colorectal and gastric cancers

Background

EpCAM is highly expressed in various cancer types of the digestive system and represent an interesting molecular therapeutic target. IMC001, an EpCAM targeted CAR-T cell therapy, showed promising anti-tumor activities in preclinical studies. Here we reported the initial dosage group in advanced GI cancers.

Methods

This first-in-human, open label, multi-centers trial involves a classic 3+3 design with separate EpCAM CAR-T cell dose escalations for monotherapy (Stage 1) and the combination with radiofrequency or microwave ablation (Stage 2) with dosage recommended by stage 1. EpCAM+ patients with relapsed or refractory digestive tumors who have no further standard treatment options and ECOG 0 or 1 are eligible to receive IMC001 at doses of 0.3, 1 or 3 million CAR-T cells/kg after lymphodepletion chemotherapy. The primary objective was to assess the safety, efficacy and cytokinetic profile of IMC001.

Results

As of 29 Apr 2022, a total of 7 patients with 4 colorectal cancers and 3 gastric cancers, received IMC001 infusion of 3×10ˆ5 cells/kg. 5 patients completed the 4 weeks of DLT follow-up visits. All patients experienced ≥G3 hematologic toxicity while no DLT was observed. The most common grade ≥3 AEs were decreases in lymphocyte, leukocyte and platelet count. One patient had a SAE of immune hepatitis occurred around 11 days after infusion of CAR-T cells and prolonged the hospitalization duration, resolved after symptomatic treatment. Grade 1 to 2 CRS were observed in 1 colorectal cancer patient and 1 gastric cancer patient. No ICANS was observed. Other adverse events related to the cell therapy were grade 1-2 of nausea, vomit, asthenia or pruritus and recovered quickly. CTC in the blood all decreased to 0 from 7 days to 4 weeks after infusion. Robust engraftment of CAR T cells and significant elevations of cytokines levels in all patients. Preliminary efficacy data showed that 4 out of 5 evaluable patients remain SD and 1 patient evaluated as PD at this lowest dosage.

Conclusions

This is the first CAR T product ever tested in human with the EpCAM target. IMC001 shows a favorable safety profile and reasonable anti-tumor activities at the initial dosage level in patients with refractory EpCAM+ cancers of digestive system. Updated data from open cohorts will be presented.

Clinical trial identification

NCT05028933, first posted: August 31, 2021. ChiCTR2100047129, first posted: June 8, 2021.

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital of Zhejiang University, Shanghai Changhai Hospital.

Funding

Suzhou Immunofoco Biotech Co., Ltd.

Disclosure

W. Fang: Personal, Principal Investigator: The First Affiliated Hospital of Zhejiang University. T. Luo: Personal, Principal Investigator: The First Affiliated Hospital of Naval Medical University/Changhai Hospital of Shanghai. Z. Lu: Personal, sub-investigator: The First Affiliated Hospital of Naval Medical University/Changhai Hospital of Shanghai. H. Zhang: Personal, sub-investigator: The First Affiliated Hospital of Zhejiang University. C. Tong: Personal, sub-investigator: The First Affiliated Hospital of Zhejiang University. S. Wang: Financial Interests, Personal, Full or part-time Employment: Suzhou Immunofoco Biotechnology Co., Ltd. F. Tang: Financial Interests, Personal, Full or part-time Employment: Suzhou Immunofoco Biotechnology Co., Ltd. G. Ai: Financial Interests, Personal, Full or part-time Employment: Immunofoco Biotech.