FDA Grants Fast Track Designation to Azer-cel in R/R DLBCL
Azer-cel elicited strong and durable responses in patients with heavily pretreated relapsed/refractory DLBCL in a phase 1b trial.
Azer-cel elicited strong and durable responses in patients with heavily pretreated relapsed/refractory DLBCL in a phase 1b trial.
The FDA has granted fast track designation to azercabtagene zapreleucel (Azer-cel), an allogenic, CD19-directed CAR T-cell therapy, for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a press release from the developer, Imugene Limited.1
Of the patients with DLBCL enrolled in the trial (n = 10), 2 patients in cohort B achieved complete responses (CRs) with azer-cel, lymphodepletion, and interleukin-2, and 1 patient in cohort A achieved a CR with azer-cel and lymphodepletion.2 As of September 3, 2024, all CRs in cohort B were durable—1 lasting for over 120 days and 1 for over 90 days—and were still ongoing.
The overall response rate (ORR) of evaluable patients (n = 9) was 44% (n = 4) with 33% (n = 3) achieving a CR; in cohort A, the ORR was 33% (n = 2) and 17% (n = 1) achieved a CR, and in cohort B, the ORR was 67% (n = 2) and 67% (n = 2) achieved a CR. In cohort A, the best time of response was less than 60 days.
Supporting results come from the open-label, dose-escalation, dose-expansion phase 1b PBCAR0191-01 trial (NCT03666000) evaluating the safety and efficacy of azer-cel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma (NHL).3
“Receiving FDA fast track designation is a testament to the transformative potential of azer-cel for patients battling relapsed/refractory DLBCL,” Leslie Chong, managing director and chief executive officer of Imugene, stated in the press release.1 “We are committed to working closely with the FDA to bring this important therapy to patients as efficiently as possible.”
The trial enrolled an estimated 129 patients; 10 of those had DLBCL, 6 of whom were in cohort A and 4 of whom were in cohort B.3 Azer-cel was administered at 6 separate dose levels: dose level 1, 3 x 105 CAR T cells/kg via intravenous injection; dose level 2, 1 x 106 CAR T cells/kg; dose level 3a, 3 x 106 CAR T cells/kg; dose level 4, 6 x 106 CAR T cells/kg in 2 administrations of 3 x 106 CAR T cells/kg after a single lymphodepletion; dose level 4b, 500 x 106 CAR T cells; and dose level 4c, 1000 x 106 CAR T cells given in 2 administrations of 500 x 106 CAR T cells on days 0 and 5.
Eligible patients had unequivocal aggressive CD-19–positive relapsed/refractory B-cell NHL confirmed by archived tumor biopsy tissue; measurable or detectable disease per the Lugano Classification; at least 2 prior lines of anti-cancer therapy for the disease under study including at least 1 chemoimmunotherapy regimen; no more than 7 lines of systemic therapy; and, of patients who received CD-19 directed CAR T therapies, no more than 2 lines of therapy after administration of prior CAR T product. NHL subtypes included DLBCL, follicular lymphoma, high-grade B-cell lymphoma, and primary mediastinal lymphoma. Additionally, patients had an ECOG performance status of 0 or 1, an estimated life expectancy of at least 12 weeks, and adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
For patients with Richter’s transformation, only 1 prior line of therapy was required for the DLBCL component.
The trial’s primary end points were the frequency of patients with azer-cel-related adverse effects (AEs) in the dose escalation and dose expansion phases, and ORR in just the dose expansion phase. Secondary end points include duration of response, progression-free survival, overall survival, time to next treatment, and the number of patients with AEs.
Regarding safety, all patients who received azer-cel and lymphodepletion demonstrated an acceptable safety profile.2 Overall, the treatment has been safe and tolerable.
References
- Azer-cel granted FDA fast track designation in blood cancer DLBCL. News release. Imugene Limited. March 19, 2025. Accessed March 20, 2025. https://tinyurl.com/4knhe9a7
- Three complete responses in azer-cel allogeneic CD19 CAR T phase 1b trial in blood cancer (diffuse large B-cell lymphoma). News release. Imugene Limited. September 3, 2024. Accessed March 20, 2025. https://tinyurl.com/33f6zzej
- Dose-escalation, dose-expansion study of safety of azer-cel (PBCAR0191) in patients with r/r NHL and r/r B-cell ALL. ClinicalTrials.gov. Updated March 10, 2025. Accessed March 20, 2025. https://tinyurl.com/49ju4t9n
Highlighting Insights From the Marginal Zone Lymphoma Workshop
Clinicians outline the significance of the MZL Workshop, where a gathering of international experts in the field discussed updates in the disease state.
