Allogeneic CAR-T Azer-Cel Achieves Complete Responses in Some Patients With Diffuse Large B-Cell Lymphoma
The cell therapy, originally developed by Precision BioSciences, is being evaluated for LBCL by Imugene.
Azercabtagene zapreleucel (azer-cel), an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, has demonstrated the ability to produce complete responses (CRs) in some patients with relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) treated in a trial run by Imugene, which licensed the therapy from Precision BioSciences.1,2
The data comes from a phase 1/1b clinical trial (NCT03666000) that has treated 10 patients thus far across 2 cohorts. In cohort A, 6 patients received the CAR-T following lymphodepletion, and in cohort B, 3 patients received the CAR-T in combination with interleukin 2 (IL-2) following lymphodepletion. One of the 4 patients treated in cohort B has not yet reached the 28 days posttreatment scan, and thus was not evaluable for efficacy. Of the 3 other patients in cohort B, 2 achieved CRs (67%), one of which has been ongoing for more than 120 days and the other of which has been ongoing for more than 90 days. The other evaluable patient in cohort B has shown stable disease, although Imugene noted that in this patient tumor decrease was seen in conjunction with an increase in signal intensity; the company noted that this may be an example of pseudoprogression and that further analysis is ongoing.
Among the 6 patients treated in cohort A, all of whom were evaluable, the overall response rate was 33%, with 1 patient (17%) achieving a CR and 1 patient achieving a partial response. It was noted that the durability of response was less than 60 days and that none of the 6 patients in this cohort remain onstudy.
Imugene characterized the safety profile of azer-cel as “safe and tolerable” so far. Notably, the patients treated in the trial had previously received 4 to 5 prior lines of therapy for their disease, including autologous CAR-T therapy for all patients. The company plans to continue recruiting patients for cohort B of the trial, and may include data from this cohort in a potential future registrational data package following a possible phase 2/3 clinical trial for the therapy in r/r DLBCL.
“I am proud of our clinical development team who assessed ways to enhance azer-cel's durability of response, as one of the biggest challenges in CAR-T therapy is ensuring that the modified T-cells stay in the body long enough to kill cancer cells,” Leslie Chong, BS, the managing director and chief executive officer of Imugene, said in a statement.1 “To maximize the response rates and durability further, we added a very low dose of IL-2 to the regimen in cohort B. We are pleased with the results, which suggest improved outcomes in patients, and we look forward to amassing more data using this dosing regimen. We will continue to seek biomarker evidence from Cohort B patients that suggest our strategy is improving the performance of azer-cel.”
Imugene originally obtained the rights to develop azer-cel in oncology from Precision BioSciences via an August 2023 transaction.2 Precision is now directing its own efforts towards the advancement of in vivo gene therapy products based on its ARCUS platform.
“We are pleased that Imugene continues to advance azer-cel toward a pivotal trial in LBCL for patients with significant unmet need,” Michael Amoroso, MBA, the chief executive officer of Precision BioSciences, said in a September 2024 statement.2 “This marks one year since our strategic decision to focus our in-house programs exclusively on in vivo gene editing and further bolsters our balance sheet, enabling us to generate Phase 1 clinical data across multiple in vivo gene editing programs starting in the first half of 2025. In the near term, we are focused on progressing our pipeline towards the clinic and remain on track to file applications with multiple global regulatory bodies for PBGENE-HBV for chronic hepatitis B later this year.”
Notably, azer-cel is also being developed for the treatment of autoimmune disease indications by TG Therapeutics, which bought rights to develop the cell therapy in such noncancer indications from Precision.3 Notably, in August 2024, the FDA cleared an investigational new drug application submitted by TG Therapeutics for azer-cel in multiple sclerosis.
