FDA Grants Fast Track Designation to ADI-001 in Relapsed/Refractory Non-Hodgkin Lymphoma

The FDA has granted a fast track designation to the CAR T-cell therapy ADI-001 for the treatment of patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

The FDA has granted a fast track designation to the CAR T-cell therapy ADI-001 for the treatment of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).1

The agent is currently under exploration in the first-in-human phase 1 GLEAN-1 trial (NCT04735471) in NHL, which announced positive interim data in December 2021.2

“Fast track designation represents an important milestone in the clinical development of ADI-001,” Chen Schor, president and chief executive officer of Adicet Bio, said in a news release. “We believe ADI-001 is unique in that it is designed to target malignant B cells by leveraging the innate and adaptive receptors found naturally on gamma delta T cells with the added benefit of an engineered anti CD20 CAR. We remain optimistic about the potential of our program and look forward to reporting additional data from the phase 1 trial of ADI-001 in the first half of 2022.”

ADI-001 is an investigational allogeneic gamma delta CAR T-cell therapy that targets malignant B cells via a CD20-directed CAR and the innate gamma delta and T-cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with a CD20-directed CAR have shown robust antitumor activity in preclinical models, leading to long-term disease stabilization.

The open-label, multi-center phase 1 study consists of 3 parts. Part 1 consists of a dose-escalation phase and will enroll approximately 30 patients with relapsed/refractory B-cell NHL. Three cell dose levels (3E7, 1E8, or 3E8) will be evaluated in part 1, using the 3 + 3 dose-escalation scheme. In part 2, approximately 36 patients will be enrolled into 3 disease-specific cohorts. Part 3 will evaluate the safety and efficacy of ADI-001 plus low-dose subcutaneous IL-2 and will enroll approximately 12 patients.3

To be eligible for enrollment, patients must have a diagnosed B-cell malignancy that has relapsed or is refractory to at least 2 prior treatment regimens, be at least 18 years of age, have an ECOG performance status of 0 or 1, and have measurable disease per Lugano 2014 and Response Evaluation Criteria in Lymphoma 2017.

The primary objective of part 1 is to determine the incidence of dose-limiting toxicity and the maximum tolerated dose (MTD) of ADI-001. In parts 2 and 3, the MTD of ADI-001 alone or in combination with IL-2 will be further evaluated for safety and antitumor activity. The secondary objectives for parts 1, 2 and 3 include the evaluation of ADI-001’s pharmacokinetics, immunogenicity, and antitumor activity alone and in combination with IL-2.

Prior results from the trial showed that as of the November 22, 2021 cutoff, 6 patients had been enrolled and received treatment with ADI-001. The first 2 patients enrolled in the lowest dose level did not reach the 28-day assessment and were not evaluable for efficacy per protocol.

Three of the four evaluable patients achieved responses, including 2 complete responses (CR) and 1 partial response (PR). Of these 4 patients, 3 received ADI-001 at the first dose level (30 million CAR+ cells) and 1 received ADI-001 at the second dose level (100 million CAR+ cells). In the first dose level, 1 patient achieved a CR, 1 patient achieved a PR, and 1 patient had progressive disease. In the second dose level, the first patient achieved a CR.

Of the 3 responders, 1 had diffuse large B-cell lymphoma and had received 5 prior lines of therapy, including 2 cycles of CD19-directed CAR T-cell therapy; 1 had follicular lymphoma transformed into a large B-cell tumor and had received 4 prior lines of therapy; and the third had mantle cell lymphoma and had received 5 prior lines of therapy.

Regarding safety, ADI-001 infusions were generally well-tolerated. No dose-limiting toxicities, graft-vs-host-disease, immune effector cell–associated neurotoxicity syndrome (ICANS) or grade 3 or higher cytokine release syndrome (CRS) had been reported by data cutoff.

Additionally, a significant increase in circulating IL-15 was reported during the first 28 days following lymphodepletion. Circulating ADI-001 was also found in the blood by quantitative polymerase chain reaction and by flow cytometry, demonstrating expansion of ADI-001. Increased levels of circulating IL-2 and IL-8 were also reported during the first 14 days after dosing, comparable with the time-to-peak for cytokines previously reported with autologous alpha-beta CAR T-cell therapy.

Notably, no meaningful increases in IL-6 were seen with ADI-001, except for 1 patient who experienced COVID-19 infection.


  1. Adicet Bio receives FDA fast track designation for lead candidate ADI-001. News release. Adicet Bio, Inc. April 19, 2022. Accessed April 20, 2022. https://bwnews.pr/3vwser0
  2. Adicet Bio announces positive interim clinical data from first-ever allogeneic, off-the-shelf, gamma delta CAR T investigational cell therapy. News release. December 6, 2021. Accessed April 20, 2022. https://bit.ly/38TCfGX
  3. Neelapu SS, Hamadani M, Stevens D, et al. A phase 1 safety and efficacy study of ADI-001 anti-CD20 CAR-engineered allogeneic gamma delta (γδ) T cells in adults with B cell malignancies, in monotherapy and combination with IL-2. Blood. 2021;138(suppl 1):2834. doi:10.1182/blood-2021-147581