The U.S. Food and Drug Administration (FDA) has granted fast track designation to the allogenic CAR T-cell therapy azer-cel (azercabtagene zapreleucel) for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma, according to news release from the drug’s manufacturer, Imugene Limited.
The FDA's fast track designation aims to facilitate drug development and expedite reviews for treatments addressing serious or life-threatening conditions with unmet medical needs, according to the release. Benefits include more frequent FDA meetings to discuss development, rolling regulatory review and potential eligibility for accelerated approval and priority review if criteria are met.
Glossary:
Immune effector cell-associated neurotoxicity syndrome: a rare side effect of CAR T-cell therapy affecting the nervous system, causing symptoms such as confusion and seizures.
Interleukin-2: a protein that boosts the growth of T cells, enhancing the effectiveness of immunotherapy.
CD19-positive: refers to cancer cells expressing the CD19 protein, making them a target for certain therapies like azer-cel.
Complete response: when all signs of cancer disappear after treatment.
Overall response rate: the percentage of patients whose cancer shrinks or disappears following treatment.
Progression-free survival: the length of time a patient's cancer does not worsen after treatment.
Overall survival: the length of time a patient survives after treatment, regardless of cancer progression.
“Receiving FDA fast track designation is a testament to the transformative potential of azer-cel for patients battling relapsed or refractory diffuse large B-cell lymphoma,” Leslie Chong, managing director and chief executive officer of Imugene, said in the release. “We are committed to working closely with the FDA to bring this important therapy to patients as efficiently as possible.”
Data from an ongoing phase 1b trial is still being evaluated, particularly in patients who have progressed on multiple prior therapies, including autologous CAR T. Azer-cel has shown a manageable safety profile, with no cases of immune effector cell-associated neurotoxicity syndrome reported in key patient groups.
According to the release, diffuse large B-cell lymphoma is the most common and aggressive form of non-Hodgkin's lymphoma, with many patients experiencing relapse or resistance to standard treatments. Azer-cel is currently being investigated as a novel therapeutic approach to address this critical unmet need.
The agent is an off-the-shelf, CD19-directed CAR T-cell therapy designed to overcome logistical challenges of autologous CAR T therapies, including prolonged manufacturing times and limited patient access. By using pre-manufactured donor T cells, azer-cel enables rapid treatment delivery.
The therapy uses a novel combination of lymphodepletion chemotherapy and interleukin-2 to improve CAR T persistence and efficacy.
More Information on the Phase 1b Trial
The ongoing trial will continue to evaluate azer-cel in patients with B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, high-grade B-cell lymphoma, marginal zone lymphoma and Waldenström macroglobulinemia, who have CD19-positive relapsed or refractory disease.
Patients are eligible for trial enrollment so long as they have received at least two prior therapies, including chemoimmunotherapy, and meet performance and life expectancy criteria. Before azer-cel, patients receive lymphodepleting chemotherapy with Fludara (fludarabine) and Cytoxan (cyclophosphamide).
The treatment is given as a single or split-dose infusion at escalating levels. Some patients receive azer-cel with interleukin 2. The study aims to assess safety and effectiveness. Patients previously treated with autologous CAR T-cell therapy must have had a response before relapse.
Previously reported data from the phase 1b trial showed that among 10 patients with relapsed or refractory DLBCL treated with azer-cel, three achieved a complete response, according to a press release from the Company. Two patients who experienced a complete response were in cohort B and received azer-cel, lymphodepletion and interleukin 2. The third patient, in cohort A, received azer-cel and lymphodepleting chemotherapy alone.
Among nine evaluable patients across cohorts A and B, the overall response rate was 44%, and the complete response rate was 33%. In cohort A, which included six patients, the overall and complete response rates were 33% and 17%, respectively. In cohort B, which included three patients, both rates were 67%. One patient in cohort B was awaiting response evaluation.
The primary end points for dose escalation and expansion are the incidence of dose-limiting toxicities and objective response rate, respectively. Secondary end points consist of complete response rate, duration of response, progression-free survival, overall survival, time to next treatment and safety.
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