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ASCO 2022 | Salvage CT041 CLDN18.2-specific CAR T-cell therapy for patients with advanced GI malignancies

Claudin 18.2 (CLDN18.2) is a highly selective cell lineage marker with limited expression in normal gastric tissues and significantly higher expression in primary gastric, pancreatic tumors and their metastases. In this interview, Gregory P. Botta, MD, PhD, UC San Diego Medical Center, San Diego, CA, discusses the results of a Phase I study evaluating salvage CT041 CLDN18.2-specific chimeric antigen receptor (CAR) T-cell therapy for patients with advanced gastric and pancreatic adenocarcinoma. These preliminary results indicate that CT041 therapy was safe and had therapeutic efficacy in patients with advanced GI cancers. In heavily pretreated gastric cancer, CT041 may have significantly improved anti-tumor activity compared to historical treatment regimens. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.

Transcript (edited for clarity)

We had presented our multi-center Phase 1b trial in the US, of salvage CT041 claudin 18.2-specific chimeric antigen receptor T-cell therapy. And this was in patients with advanced gastric and pancreatic adenocarcinoma, so they would’ve had to have two prior lines of gastric cancer treatment and one prior line of pancreatic adenocarcinoma treatment.

The idea is, is that claudin 18.2 is a highly selective and expressed self-surface marker in GI cancers, gastric, GE junction and pancreas cancer...

We had presented our multi-center Phase 1b trial in the US, of salvage CT041 claudin 18.2-specific chimeric antigen receptor T-cell therapy. And this was in patients with advanced gastric and pancreatic adenocarcinoma, so they would’ve had to have two prior lines of gastric cancer treatment and one prior line of pancreatic adenocarcinoma treatment.

The idea is, is that claudin 18.2 is a highly selective and expressed self-surface marker in GI cancers, gastric, GE junction and pancreas cancer. So based on results from a Phase 1 trial in China, a Phase 1b trial in North America initiated. And it’s currently open at four, soon to be six, centers. And the idea was to try and use CAR-T in solid tumors.

CAR-T in solid tumors has a variety of obstacles that need to be overcome. The first is acquiring a target that is specifically and highly expressed on tumor tissue and not on normal tissue, so that we can have on-target on-tumor effects instead of on-target off-tumor effects. I think that’s where a lot of solid tumor CAR-T has been hampered.

The other thing is, is that when you infuse the CAR-T into the bloodstream, unlike hematologic cancers that are there at the interface, the CAR-T cells in solid tumors have to diffuse or transit out of the blood stream into the solid tumor. So obviously there’s a obstacle for that transition, but also the penetration into bulky tumors. So there’s a lot of different things that need to become realized in solid tumor CAR-T for them to be efficacious.

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