Adicet soars on early responses to gamma delta CAR-T therapy

Adicet Bio has laid down a marker for the nascent gamma delta CAR-T cell therapy space, reporting its off-the-shelf candidate ADI-001 triggered responses in a small clinical trial of B-cell non-Hodgkin lymphoma (NHL) patients. Shares in Adicet jumped 45% to above $14 in premarket trading.

The potential for gamma delta cells to persist after treatment, recognize and kill circulating tumor cells, and infiltrate and take out solid tumors has attracted a clutch of companies. Adicet is the first of the companies to present clinical data on an off-the-shelf gamma delta CAR-T cell therapy, making it an early test case for the potential of the cells.

Investigators enrolled heavily pretreated NHL patients in the study of the CD20 therapy. Participants had received a median of five prior lines of systemic therapy. One patient had previously received an autologous CD19 CAR-T therapy. 

The first two patients enrolled at the lowest dose level tested did not reach the Day 28 assessment. Of the next three patients to receive the lowest dose, one person’s disease progressed but the other two subjects responded. Adicet saw one complete response (CR) and one partial response, which it called a near CR, in the lowest-dose cohort. The complete response happened in a patient previously treated with Bristol Myers Squibb’s CD19 CAR-T Breyanzi.

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Adicet also has data on one patient who received the next dose, which contained more than three times as many cells. That patient had a complete response. Adicet excluded the two non-evaluable patients from its analysis for a per-protocol overall response rate (ORR) of 75% and a CRR of 50%. Including the two patients brings the ORR down to 50%.

It is possible the ORR and CRR will fall as more patients are enrolled in the study. However, there is also potential for Adicet to maintain or improve the response rate. Adicet is yet to see dose-limiting toxicities, graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome or grade 3 or higher cytokine release syndrome.

“The preliminary safety and efficacy data from low-dose ADI-001 collected to date indicate the potential for a broad therapeutic window,” Francesco Galimi, M.D., Ph.D., chief medical officer at Adicet, said in a statement.

Adicet is now assessing how ADI-001 fares when given at higher doses. The plan is to include three cohorts in the dose-escalation stage of the study. Most of the available data come from the lowest of the dose cohorts. Once Adicet has established the optimal dose, it will run a dose-expansion study. The next data drop is scheduled for the first half of next year.