EHA 2022 – Crispr’s second off-the-shelf Car-T disappointment

Crispr Therapeutics has seen impressive activity in heavily pretreated patients with T-cell lymphoma, a tough malignancy, given its CD70-directed allogeneic Car-T therapy CTX130. Unfortunately, this project has been hit with the same relapse problems as Crispr’s own and others’ off-the-shelf Cars: of the nine remissions in the company’s Cobalt-Lym trial reported at the EHA meeting on Saturday just one can be said to be long-lasting, a PR of eight months’ duration from CTX130 infusion. One short-term response is ongoing without further intervention, while one was achieved only after a second Car-T cell infusion. The remaining six responses have all relapsed, though three were retreated, and two of these went on to be transplanted. As such, Crispr’s headline ORR number of 50% across all doses, or 70% at level 3 or above, does not tell the whole story. Investors in all allo Car-T companies will be used to this story, with Caribou falling into the relapse trap just last Friday. Crispr itself has already suffered this fate with its lead off-the-shelf Car, CTX110, which hits CD19. Allogene, whose anti-CD70 Car ALLO-316 is in phase 1 for kidney cancer, will pay particularly close attention.