CAR T-Cell Therapy Shows Efficacy and Safety in B-Cell Malignancies
Adicet Bio reported positive interim data from the phase 1 GLEAN study.
Treatment with the chimeric antigen receptor (CAR) T-cell therapy ADI-001 elicited complete and near complete responses in patients with B-cell Non-Hodgkin’s Lymphoma, according to interim data from the phase 1 GLEAN study (NCT04735471) announced by Adicet Bio.
“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 Chen Schor, president and chief executive officer, Adicet Bio, in a statement. "Data to-date suggest that ADI-001 is highly clinically active. We look forward to reporting additional data in the first half of 2022 and to rapidly progressing our pipeline to realize the full potential of our gamma delta CAR T cell platform for patients.”
The GLEAN study is primarily evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and optimal dosing of ADI-001. It has enrolled and treated 6 of an expected 75 patients as of November 22, 2021, 4 of which were evaluable. Of these patients, 2 experienced complete responses (CR) and 1 experienced a partial response (PR) which was characterized as a near complete response.
Enrolled patients were heavily pretreated, with a median of 5 lines of prior systemic therapy. Responders had diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Responders were received 30 million CAR+ cells (n =3) and 100 million CAR+ cells (n = 1).
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“The unequivocal responses to ADI-001 in this heavily pre-treated patient population at such low dose levels are highly promising," Sattva Neelapu MD, professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, added to the statement. “These data suggest that ADI-001 has the potential to be an effective treatment option for B cell malignancies if confirmed in further clinical testing. ADI-001 does not require gene editing and provides complementary innate, adaptive, and CAR mediated antitumor effects which may improve durability and minimize emergence of tumor resistance.”
ADI-001 was relatively well-tolerated, with no dose-limiting toxicities, graft vs host disease, or immune effector cell-associated neurotoxicity syndrome observed, as well as no cytokine release syndrome greater than grade 2.
Investigators observed promising pharmacokinetics of ADI-001, with a significant increase in circulating IL-15 in the 28-days after lymphodepletion. ADI-001 was seen to expand in participants, as observed by quantitative polymerase chain reaction and by flow cytometry measuring the emergence of the product in the blood. Elevations in IL-2 and IL-8 were observed in the first 14 days post-dosing but no meaningful increases in IL-6 related to treatment were seen, except in 1 participant who experienced COVID-29 infection.
“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,” Francesco Galimi, MD, PhD, senior vice president and chief medical officer, Adicet Bio, added to the statement. "As we look to expand into additional cohorts, we plan to leverage our scalable off-the-shelf manufacturing process to meet future needs. We look forward to advancing our novel allogeneic gamma delta T cell pipeline for cancer patients.”
