Adicet Bio Announces Positive Interim Clinical Data From First-Ever Allogeneic, Off-The-Shelf, Gamma Delta CAR T Investigational Cell Therapy
- Complete and near complete responses observed with ADI-001 starting at lowest dose level in Phase 1 study for the treatment of B-cell Non-Hodgkin’s Lymphoma (ORR=75%, CR=50%)
- No ADI-001-related serious adverse events, including GvHD, neurotoxicity or high-grade CRS have been reported to date
- Evidence of in vivo expansion and circulating pharmacodynamic biomarkers consistent with ADI-001 activation
- Favorable safety and clinical activity reinforces the potential of Adicet’s first-in-class allogeneic, off-the-shelf gamma delta CAR T cell platform
- Company to hold webcast today at 5:30am PT /
As of the
“We are extremely excited to see such profound early complete responses in our Phase 1 dose-finding study evaluating ADI-001 as monotherapy among patients with very advanced cancer starting at our first dose level of 30 million CAR+ cells," said
“The unequivocal responses to ADI-001 in this heavily pre-treated patient population at such low dose levels are highly promising," said Sattva Neelapu M.D., Professor in the
Of the four efficacy evaluable patients, three received ADI-001 at dose level one (30 million CAR+ cells) and one received ADI-001 at dose level two (100 million CAR+ cells). In dose level one, one patient achieved a CR, one patient achieved a PR that was characterized as near CR and one patient had progressive disease (PD). In dose level two, the first patient achieved a CR.
All evaluable patients had been heavily pre-treated with a median of five lines of prior systemic therapies. Of the three patients who achieved PR or better under Lugano 2014 criteria (ORR=75%, CR=50%), one had diffuse large B-cell lymphoma (DLBCL) with five prior lines of therapy including two cycles of anti-CD19 CAR T cell therapy, one had follicular lymphoma transformed into a large B-cell tumor with four prior lines of therapy, and the third had mantle cell lymphoma with five prior lines of therapy. These patients achieved two CRs and a near CR.
Overall, ADI-001 infusions were generally well-tolerated. No dose-limiting toxicities, graft vs host disease (GvHD), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or grade 3 or higher Cytokine Release Syndrome (CRS) have been reported to-date, suggesting a potentially wide therapeutic window for ADI-001.
A significant increase in circulating IL-15 was observed during the 28-day window following lymphodepletion, potentially providing cytokine support for the proliferation of ADI-001. Emergence of circulating ADI-001 in the blood was observed by quantitative polymerase chain reaction and by flow cytometry, demonstrating expansion of ADI-001 in patients. Elevations in additional circulating cytokines, primarily IL-2 and IL-8 were observed during the first 14 days from dosing, consistent with the activation profile of ADI-001 and similar to the observed time-to-peak for cytokines previously reported in association with autologous alpha-beta CAR T cells. Importantly, no meaningful increases in IL-6 were seen in association with ADI-001, except for one patient who experienced COVID-19 infection, suggesting reduced likelihood for ICANS and high-grade CRS.
“It is remarkable to see our early preclinical studies translate to the clinic. The preliminary safety and efficacy data from low-dose ADI-001 collected to date indicate the potential for a broad therapeutic window. Without the need for gene editing and its associated safety concerns, our platform is designed to preserve the natural innate and adaptive anti-tumor activity of gamma delta CAR T cells, which we believe may lead to better durability,” said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of
Table 1: Summary of ADI-001 interim data from two dosing cohorts*:
|Dose Level||Age/Sex||B-cell lymphoma subtypes||# Prior lines of therapies||Prior CAR T?||Best Response (BOR) by Lugano Criteria (2014)|
|30 million CAR+ cells
(from chronic lymphocytic leukemia)
|5 prior lines||No||PD|
|66/F||Transformed high grade
B cell tumor (from follicular lymphoma)
|4 prior lines
|75M||DLBCL||5 prior lines||Yes (liso-cel)||CR|
|100 million CAR+ cells||62/M||Mantle cell lymphoma||5 prior lines||No||CR|
*Efficacy evaluable patients as of November 22, 2021 database entry. Data are subject to further review and verification.
Webcast/Conference Call Information
Adicet will host a live presentation on
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 (615) 622-8057 (international) and reference the conference ID 6952318. The archived webcast will be available on the Company's website beginning approximately two hours after the event.
ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a treatment for B-cell non-Hodgkin's lymphoma. 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 antitumor activity in preclinical models, leading to long-term control of tumor growth.
About the GLEAN Study
This Phase I 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).
This press release contains "forward-looking statements" of Adicet within the meaning of the Private Securities Litigation Reform Act of 1995 relating to business and operations of Adicet. These forward-looking statements include, but are not limited to, express or implied statements regarding Adicet’s beliefs and expectations regarding: the interim clinical data resulting from its Phase 1 study of ADI-001, including the expected potential therapeutic effects, safety and tolerability profile, design, implementation, timing, and success of ADI-001; and expectations regarding the potential of its other CAR gamma delta T cell therapy development activities.
Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including without limitation, the effect of COVID-19 on our business and financial results, including with respect to disruptions to our clinical trials, business operations, and ability to raise additional capital; Adicet's ability to execute on its strategy; that positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; future clinical studies may fail to demonstrate adequate safety and efficacy of our product candidates, which would prevent, delay, or limit the scope of regulatory approval and commercialization; regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time–consuming, and inherently unpredictable; regulatory developments in
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Source: Adicet Bio