FDA Grants Fast Track Designation to Azer-Cel for R/R DLBCL

The FDA has granted fast track designation to the allogeneic CAR T-cell therapy azercabtagene zapreleucel (azer-cel; PBCAR0191) as a potential therapeutic option for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).¹

The off-the-shelf CD19-directed CAR T-cell therapy is currently being evaluated in a phase 1b trial (NCT03666000) in patients with relapsed/refractory non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia.

“Receiving FDA fast track designation is a testament to the transformative potential of azer-cel for patients [experiencing] relapsed or refractory DLBCL,” Leslie Chong, managing director and chief executive officer of Imugene Limited, stated in a news release. “We are committed to working closely with the FDA to bring this important therapy to patients as efficiently as possible.”

Previously reported data from the phase 1b trial demonstrated that among patients with relapsed/refractory DLBCL treated with azer-cel (n = 10), 3 achieved a complete response (CR).² Two patients to experience a CR were treated in cohort B with azer-cel, lymphodepletion, and interleukin 2 (IL-2). The third patient to achieve a CR was enrolled in cohort A, where they received azer-cel and lymphodepleting chemotherapy alone. The CRs reported in cohort B had durations of more than 120 and more than 90 days, respectively.

Among all evaluable patients between cohorts A and B (n = 9), the overall response rate (ORR) was 44%, and the CR rate was 33%. In cohort A (n = 6), the ORR and CR rates were 33% and 17%, respectively. These respective rates were both 67% in cohort B (n = 3). Notably, 1 patient in cohort B was awaiting response evaluation.

As of data cutoff, all patients enrolled in cohort B (n = 4) were ongoing on the study, and investigators planned to enroll additional patients to this cohort.

All patients enrolled in the trial had received 4 or 5 prior lines of therapy, including autologous CAR T-cell therapies. Safety data showed azer-cel was tolerable.

In the ongoing nonrandomized, open-label, dose-escalation and -expansion trial, patients with B-cell non-Hodgkin lymphoma are required to have CD19-positive relapsed/refractory disease.³ During dose escalation, eligible histologies comprise DLBCL, including Richter transformation; follicular lymphoma (FL), including grade III or transformed FL; high-grade B-cell lymphoma (HBCL); or primary mediastinal lymphoma. In dose expansion, patients are required to have DLBCL not otherwise specified; HBCL; DLBCL transformed from FL; marginal zone lymphoma; or Waldenström macroglobulinemia.

Those with non-Hodgkin lymphoma are also required to have measurable or detectable disease per Lugano criteria; at least 2 prior lines of anticancer therapy, including at least 1 chemoimmunotherapy regimen; and no more than 7 prior lines of therapy. In dose-expansion only, prior autologous CAR T-cell therapy is required with a demonstrated clinical response at day 28 or later, followed by relapse or progression. An ECOG performance status of 0 or 1 and a life expectancy of at least 12 weeks are required for all patients.

Prior to azel-cel, patients are receiving lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide. In the first 3 arms, azer-cel is being 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 is being given as 2 infusions at 3 x 10⁶ CAR T cells for a target total of 6 x 10⁶ CAR T cells. Patients being treated at dose level 4b are receiving a single infusion of the CAR T-cell therapy at 500 x 10⁶ CAR T cells plus IL-2, and those being treated at dose level 4c are being administered 2 infusions of azer-cel at 500 x 10⁶ CAR T cells on days 0 and 5.

The primary end points for dose escalation and expansion are the incidence of dose-limiting toxicities and ORR, respectively. Secondary end points consist of CR rate, duration of response, progression-free survival, overall survival, time to next treatment, and safety.

References

1. Azer-cel granted FDA fast track designation in blood cancer DLBCL. News release. Imugene. March 19, 2025. Accessed March 20, 2025. https://company-announcements.afr.com/asx/imu/cb54785a-0444-11f0-9779-b6359b194da9.pdf
2. 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 20, 2024. https://app.sharelinktechnologies.com/announcement/asx/9ec9d95529ab3adb318296ee5b344164
3. 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://clinicaltrials.gov/study/NCT03666000