ASCO: Adicet's gamma delta CAR-T therapy readout paves way for pioneering phase 2 trial

Adicet Bio’s gamble on the nascent gamma delta CAR-T cell therapy space seems to be paying off, with the latest phase 1 readout showing its drug is safe and potentially effective. The biotech can now start to plan for a mid-stage trial of the pioneering medicine.

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 in the form of ADI-001, making the drug an early test case for the potential of the cells.

Building on previous data published in December, an analysis of eight patients with relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) showed that ADI-001 demonstrated a 75% overall response rate (ORR) and complete response (CR) across all three dose levels.

The patients, who on average had previously received four cancer therapies, had a poor prognostic outlook, the biotech said in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting June 6. Of the four patients who could be evaluated six months after treatment, half had remained cancer-free.

One of these two cancer-free patients had previously relapsed after two treatments with an autologous anti-CD19 CAR-T therapy, suggesting Adicet’s drug had provided a “major clinical benefit,” said Sattva Neelapu, M.D., professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, in a statement.

“When we look at the totality of these early data, we have an indicator that allogeneic gamma-delta CAR T cell therapy like ADI-001 could be a significant advance,” Neelapu said.

ADI-001 was well tolerated in the study, with no occurrences of dose-limiting toxicities, graft vs host disease, or grade 3 or higher cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome reported, the company said.

“Adicet is a pioneer in the field of gamma delta CAR-T cell therapies and it is gratifying to see the highly encouraging clinical data for ADI-001 unfold as a potential best-in-class therapy for NHL,” said Adicet Bio CEO Chen Schor. “Notably, with a favorable safety and tolerability profile, treatment to date with ADI-001 demonstrated an impressive [complete response] rate, including 100% in CAR-T relapsed patients and very encouraging durability of response.”

Adicet expects to identify a recommended dose for a phase 2 trial in the second half of 2022, with at least one “potentially pivotal” study to launch in the first half of 2023.