FDA Grants Azer-Cel Fast Track Status in DLBCL
Azercabtagene zapreleucel has been granted fast track designation from the FDA for the treatment of diffuse large B-cell lymphoma.
US FDA
- The FDA granted fast track designation to azercabtagene zapreleucel (azer-cel; PBCAR0191) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
- Azer-cel is an allogeneic chimeric antigen receptor (CAR) T-cell therapy.
- An ongoing trial (NCT03666000) is currently evaluating the agent in patients with B-cell non-Hodgkin lymphoma with CD19-positive relapsed/refractory disease.
The FDA has granted azer-cel, an allogeneic, off-the-shelf CD19-directed CAR T-cell therapy, fast track designation for the treatment of patients with relapsed/refractory DLBCL.1
A phase 1b trial (NCT03666000) is currently underway to evaluate azer-cel in patients with relapsed/refractory non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia.2 The multicenter, nonrandomized, open-label, dose-escalation and dose-expansion trial is evaluating the agent’s safety and clinical efficacy in those with B-cell non-Hodgkin lymphoma who have CD19-positive relapsed/refractory disease.
Investigators are also looking to find an appropriate dose of azer-cel to optimize safety and efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma.
“Receiving FDA fast track designation is a testament to the transformative potential of azer-cel for patients [experiencing] relapsed or refractory DLBCL,” said Leslie Chong, managing director and chief executive officer of Imugene Limited, in a press release.1 “We are committed to working closely with the FDA to bring this important therapy to patients as efficiently as possible.”
Microscopic examination revealing red blood cells, white blood cells, neutrophils, eosinophils: ©AkuAku - stock.adobe.com
In the phase 1b study, patients with DLBCL, including Richter transformation; follicular lymphoma (FL), including grade III or transformed FL; high-grade B-cell lymphoma; or primary mediastinal lymphoma. In dose expansion, patients are required to have DLBCL not otherwise specified; high-grade B-cell lymphoma; DLBCL transformed from FL; marginal zone lymphoma; or Waldenström macroglobulinemia, will be included in the dose-escalation portion.2 Enrollment in this portion of the trial is also open to patients with non-Hodgkin lymphoma who have measurable or detectable disease per Lugano criteria. Patients must have received 2 or more prior lines of anticancer therapy, including at least 1 chemoimmunotherapy regimen, and no more than 7 prior lines of therapy.
The dose-expansion portion of the study, patients must have received prior autologous CAR T-cell therapy and have demonstrated a clinical response at day 28 or later, followed by relapse or progression.
All patients are also required to have an ECOG performance status of 0 or 1, a life expectancy of 12 weeks or more, and adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
Patients will receive lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide before treatment with azer-cel. In the first 3 arms, azer-cel will be given as a single infusion at escalating doses of 3 x 105 CAR T cells, 1 x 106 CAR T cells, or 3 x 106 CAR T cells. At dose level 4, azer-cel will be given to patients as 2 infusions at 3 x 106 CAR T cells for a target total of 6 x 106 CAR T cells. At dose level 4b, patients will receive a single infusion of the CAR T-cell therapy at 500 x 106 CAR T cells plus interleukin 2 (IL-2). Patients treated at dose level 4c will be given 2 infusions of azer-cel at 500 x 106 CAR T cells on days 0 and 5.
For dose-escalation and -expansion portions of the study, the primary end points include the incidence of dose-limiting toxicities and overall response rate (ORR). Secondary end points consist of complete response (CR) rate, duration of response, progression-free survival, overall survival, time to next treatment, and safety.
Prior Findings From the Phase 1b Study of Azer-Cel
Findings from the prior phase 1b trial showed that of the 10 patients with relapsed/refractory DLBCL treated with azer-cel, 3 achieved a CR, 2 of whom were treated in cohort B with the azer-cel, lymphodepletion, and IL-2 combination.3 In this cohort, the CRs reported had durations of more than 120 days.
The third patient who had a CR was enrolled in cohort A, where they were treated with azer-cel and lymphodepleting chemotherapy alone. In this cohort, the CR reported had a duration of more than 90 days.
Between cohorts A and B, all 9 evaluable patients had an ORR of 44%. Here, the CR rate was 33%. In cohort A (n = 6), azer-cel demonstrated ORR and CR rates of 33% and 17%, respectively. Cohort B (n = 3) showed stronger efficacy signals with both ORR and CR at 67%, though 1 patient remained awaiting response assessment at data cutoff.
Notably, all cohort B patients (n = 4) remained on treatment at the time of analysis, prompting investigators to expand enrollment in this cohort. The heavily pretreated population, which consisted of having 4 to 5 prior lines, including autologous CAR T, tolerated azer-cel well. Further, the agent had a manageable safety profile.
REFERENCES
Azer-cel granted FDA fast track designation in blood cancer DLBCL. News release. Imugene. March 19, 2025. Accessed March 24, 2025. https://tinyurl.com/2f9efr4k
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 24, 2025. https://clinicaltrials.gov/study/NCT03666000
Three complete responses in azer-cel allogeneic CD19 CAR T phase 1b trial in blood cancer (diffuse large B-cell lymphoma). News release. Imugene. September 2, 2024. Accessed March 24, 2024. https://tinyurl.com/4m37u3ys
