On June 6, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapies for cancer, reported emerging positive safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6, 2022 (Press release, Adicet Bio, JUN 6, 2022, View Source [SID1234615620]). The presentation outlines a summary of clinical data as of a May 31, 2022, data-cut date.
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"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 Chen Schor, President and Chief Executive Officer of Adicet Bio. "Notably, with a favorable safety and tolerability profile, treatment to date with ADI-001 demonstrated an impressive CR rate, including 100% in CAR-T relapsed patients, and very encouraging durability of response. We look forward to discussing the data in more detail and outlining next steps in our webcast this afternoon."
"It is impressive to see 50 percent of six-month evaluable patients cancer free beyond seven months. One of these patients had previously relapsed after two treatments with autologous anti-CD19 CAR T and now remains cancer free seven and a half months following administration of ADI-001, suggesting the patient has had major clinical benefit from ADI-001. This is particularly notable because patients who relapse after autologous anti-CD19 CAR T have dismal outcomes with a median survival of approximately six months," said Sattva Neelapu, M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "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."
"NHL remains a disease that is very difficult to treat, especially in high-risk patients with aggressive disease. Our study is enrolling patients with aggressive B-cell lymphoma, including patients with double-hit and triple-hit high-grade B cell lymphoma and patients who had a prior relapse to autologous anti-CD19 CAR T therapy," said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "We are encouraged by the CRs observed to date in the Phase 1 study and are committed to rapidly advancing ADI-001 into a potential pivotal program."
Data highlights as of the May 31, 2022 data-cut date included in the ASCO (Free ASCO Whitepaper) presentation are as follows:
Of the eight evaluable patients, three received ADI-001 at dose level 1 (30 million CAR+ cells), three received ADI-001 at dose level 2 (100 million CAR+ cells) and two received ADI-001 at dose level 3 (300 million CAR+ cells). There are currently no patients with indolent lymphoma, such as follicular lymphoma, enrolled in the study.
Patients were heavily pretreated with a median number of prior therapies of 4 (range 2-5) and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of 4 (range 2-5).
ADI-001 treatment demonstrated a 75% overall response rate (ORR) and complete response (CR) in the study across all dose levels. In dose levels 2 and 3 combined, ADI-001 demonstrated an 80% ORR and CR rate.
In three patients that previously relapsed after prior autologous anti-CD19 CAR T therapy, treatment with ADI-001 demonstrated 100% ORR and CR rate. These patients included a triple-hit high grade B-cell lymphoma patient with prior exposure to Liso-cel, as well as a DLBCL patient and a double-hit high grade B-cell lymphoma patient who had previously achieved a PR to Axi-cel.
Early data indicate encouraging durable anti-tumor responses with potential for dose related increase in durability. 50% (2 of 4) of evaluable patients with at least six months follow up remain cancer free.
Detection of circulating ADI-001 in the blood by flow cytometry indicated in vivo expansion and dose-related increase of ADI-001 exposure in patients.
ADI-001 was well tolerated in the study to date. There were no occurrences of dose-limiting toxicities, graft vs host disease (GvHD), or Grade 3 or higher Cytokine Release Syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) reported. There were no infections associated with enhanced lymphodepletion (eLD).
Table 1: Summary of ADI-001 interim data from three dosing cohorts: *
*Efficacy-evaluable patients as of the May 31, 2022 data-cut date. Data are subject to further review and verification. BOR= best overall response. PD=progressive disease.
Table 2: ADI-001 Preliminary Efficacy Data:
(Per protocol analysis, independent radiographic assessment using Lugano 2014)
*Efficacy-evaluable patients as of the May 31, 2022, data-cut date. Data are subject to further review and verification.
As of the May 31, 2022, data-cut date, of the six patients who achieved CR:
Dose level 1:
As previously disclosed, one patient administered ADI-001 in dose level 1, a 66-year-old female who had achieved a CR, developed COVID-19 related pneumonia approximately two and a half months after ADI-001 administration and later died of complications from it, unrelated to ADI-001. This patient was previously reported as a partial response (PR) by local radiological assessment and has been assessed as a CR by independent central reading.
One patient with triple-hit high grade B-cell lymphoma in dose level 1 who had relapsed following two prior treatments with autologous anti-CD19 CAR T therapy, had a CR after treatment with ADI-001. The patient developed a local skin relapse at four months, and was administered local radiotherapy. The skin lesion resolved with no systemic therapy provided to the patient. The patient continues to be cancer free seven and a half months following administration of ADI-001, as measured by a negative PET/CT scan.
Dose level 2:
Both patients administered ADI-001 in dose level 2 have ongoing CR. One patient has a CR beyond seven months and one patient has a CR beyond four and a half months.
Dose level 3:
Both patients administered ADI-001 in dose level 3 have ongoing CR with follow-up beyond three and one month, respectively.
In summary, 50% of evaluable patients with at least six months follow up (2 of 4) remain cancer free.
Table 3: ADI-001 Preliminary Safety Data in Efficacy-Evaluable Patients+
+Safety assessment was performed using the Common Terminology Criteria for Adverse Events (v5) and the American Society for Transplantation and Cellular Therapy criteria. The two ADI-001-related adverse events of special interest (AESI) were a Grade 1 CRS at DL1 and a Grade 1 ICANS at DL2, which resolved within 24 hours without medical intervention; No DLTs or GvHD; No treatment discontinuations due to AEs; two patients administered standard lymphodepletion (sLD) and six patients eLD; There were no eLD-associated clinical infection.
*One patient in DL 1 who received sLD developed COVID-19 pneumonia later died of complications of it, unrelated to ADI-001.
Given the safety profile to date, the protocol was amended to include a new DL 4 (1E9 CAR+ cells) and a potential ADI-001 consolidation dosing at DL3 to finalize the recommended Phase 2 dose in the second half of 2022. The Company expects to provide at least one additional clinical update for the ADI-001 Phase 1 study in the second half of 2022. The Company will discuss with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) the design of two pivotal intent studies and a potential path to support a Biologics License Application (BLA) and Marketing Authorization Application (MAA) for ADI-001 and initiate at least one potentially pivotal study in the first half of 2023.
Details of the ASCO (Free ASCO Whitepaper) Oral Presentation:
Abstract Number: 7509
Abstract Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T cells in Adults with B-cell Malignancies
Presenting Author: Sattva Neelapu, M.D., The University of Texas MD Anderson Cancer Center
Session Type/Title: Clinical Science Symposium/ Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Date: Monday, June 6, 2022
Time: 8:00 AM-9:30 AM CDT
Webcast/ Conference Call information
The Company will host a conference call and webcast today, June 6, 2022, at 4:30pm ET to discuss the results. The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or +1 (615) 622-8057 (international) and referencing the conference ID 5466375. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.
About ADI-001
ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent anti-tumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.
About the GLEAN Study
This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).