AZD6422 / AstraZeneca, AbelZeta Pharma - LARVOL DELTA

Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancer. (PubMed, Clin Cancer Res) - "AZD6422 was safe and efficacious in patient-derived, CLDN18.2-positive murine models of gastrointestinal cancers. Our data support further clinical development of AZD6422 for patients with these cancers."

CAR T-Cell Therapy • Journal • Preclinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18 • TGFB1

Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancer (Clin Cancer Res) - "AZD6422 exhibited significant antitumor activity and tolerability in multiple patient-derived tumor xenograft models with various CLDN18.2 and TGF-β levels, as determined by immunohistochemistry. Efficacy of armored CAR-Ts in tumor models with elevated TGF-β was increased in vitro and in vivo. In vitro restimulation assays established greater persistence and cytolytic function of AZD6422 compared with a traditionally manufactured CAR-T."

Preclinical • Esophageal Cancer • Gastric Cancer • Pancreatic Cancer

Utilization of CLDN18.2 syngeneic mouse models to study chimeric antigen receptor T cells in immunocompetent mice (AACR 2024) - "This expression profile renders CLDN18.2 an ideal tumor associated antigen (TAA) for CAR-T targeting and an armored targeted CAR-T, AZD6422, is in clinical development...​ This syngeneic mouse model platform will additionally allow us to investigate how mCAR-T cells perform within a fully competent TME in combination with other therapeutic agents targeting cancer cells via altered mechanism of action. ​"

CAR T-Cell Therapy • IO biomarker • Preclinical • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Peking University | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CLDN18

Preclinical evaluation and anti-tumor activity of AZD6422, a CLDN18.2 targeting armored CAR-T for gastric, esophageal and pancreatic cancers (SITC 2023) - "2 and TGFβ levels as determined by IHC. Conclusions Taken together, the selection of CAR-T design which provided therapeutic margin in relevant murine models, addition of armoring and optimization of manufacturing enabled generation of a lead molecule which provides efficacy in relevant cell line and patient derived xenograft models of gastric, pancreatic and esophageal cancers and supports further clinical development of AZD6422."

IO biomarker • Preclinical • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18 • TGFB1

Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors (clinicaltrials.gov) - P1 | N=96 | Not yet recruiting | Sponsor: Peking University

Metastases • New P1 trial • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CLDN18