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Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results
Changsong Qi1, Jifang Gong1, Jian Li1
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Abstract:
Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 108, 3.75 × 108 or 5.0 × 108 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.
Insights
Chimeric antigen receptor (CAR) T cell therapy shows promise for solid tumors. Claudin18.2-targeted CAR T cells (CT041) demonstrated significant efficacy and an acceptable safety profile in patients with advanced digestive system cancers, especially gastric cancer.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T cell therapy has shown success in hematologic malignancies but faces limitations in solid tumors.
- Claudin18.2 (CLDN18.2) is a promising target for gastric cancer and other digestive system cancers.
- Preclinical studies indicated CLDN18.2-redirected CAR T cells have potential efficacy against gastric cancer.
Purpose of the Study:
- To evaluate the safety and efficacy of CLDN18.2-targeted CAR T cells (CT041) in a phase 1 clinical trial.
- To assess CT041's pharmacokinetics and immunogenicity in patients with previously treated, CLDN18.2-positive digestive system cancers.
- To determine the overall response rate (ORR), disease control rate (DCR), and survival outcomes.
Main Methods:
- An ongoing, open-label, single-arm, phase 1 clinical trial (NCT03874897) involving 37 patients.
- Patients received one of three doses of CT041: 2.5 × 10^8, 3.75 × 10^8, or 5.0 × 10^8 cells.
- Primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.
Main Results:
- All patients experienced grade 3 or higher hematologic toxicity; 94.6% had grade 1 or 2 cytokine release syndrome (CRS).
- No grade 3 or higher CRS, neurotoxicities, treatment-related deaths, or dose-limiting toxicities were reported.
- The overall response rate (ORR) was 48.6%, disease control rate (DCR) was 73.0%, and 6-month duration of response was 44.8%.
Conclusions:
- CT041 demonstrates promising efficacy with an acceptable safety profile in heavily pretreated patients with CLDN18.2-positive digestive system cancers.
- Patients with gastric cancer showed particularly strong responses, with an ORR of 57.1% and a 6-month overall survival rate of 81.2%.
- These interim results support further investigation of CT041 for CLDN18.2-positive solid tumors.
