Three Complete Responses in Azer-Cel CD19 CAR T Phase 1b Blood Cancer Trial

Imugene Limited, a clinical-stage immuno-oncology company, has reported encouraging outcomes from its Phase 1b clinical trial involving azer-cel (azercabtagene zapreleucel), an allogeneic off-the-shelf CD19 CAR T treatment. This trial targeted patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), a severe form of non-Hodgkin’s lymphoma (NHL). The patient group consisted of individuals whose cancer had recurred following prior autologous CAR T therapy, highlighting a significant unmet medical need.

In Cohort B of the trial, the first two patients experienced complete responses (CR), maintaining these responses for over 120 days and 90 days respectively. All four patients in this cohort had failed four to five previous treatments, including autologous CAR T therapy. Despite these prior failures, they have continued their participation in the trial, showcasing the robustness and durability of the responses. Imugene plans to enroll more patients in this cohort and monitor their progress.

A total of ten patients have been treated across Cohorts A and B. Cohort A included six patients who received azer-cel in conjunction with lymphodepletion (chemotherapy). Meanwhile, Cohort B involved four patients who received azer-cel, lymphodepletion, and a low dose of interleukin 2 (IL-2). The addition of IL-2 was aimed at enhancing the durability of response, as IL-2 aids T-cells in growth and survival, thereby potentially improving the efficacy of CAR T cells.

The trial is being conducted across 15 prominent cancer centers in the United States, including Columbia University, University of Minnesota, Emory, and Moffitt Cancer Centers, with plans to expand to additional sites in Australia.

Among the nine evaluable patients from both cohorts, six were from Cohort A, where one patient achieved a complete response and another a partial response, resulting in an overall response rate (ORR) of 33%. The durability of response in Cohort A was less than 60 days, and none of these patients remain in the trial. In Cohort B, three evaluable patients showed two complete responses, giving an ORR and CR rate of 67%. One patient in this cohort displayed stable disease with a notable decrease in tumor size, potentially indicative of pseudoprogression due to T-cell infiltration. The durability of responses in Cohort B was greater than 120 and 90 days respectively, with all four patients, including one awaiting a 28-day scan, still participating in the trial.

Imugene's Chief Medical Officer, Dr. Paul Woodard, expressed optimism about the promising results in Cohort B, emphasizing the durability of the complete responses. Leslie Chong, Managing Director and CEO of Imugene, highlighted the strategic addition of IL-2 to the treatment regimen in Cohort B, which appears to have improved patient outcomes. The company plans to continue enrolling patients in Cohort B and aims to gather comprehensive data for a potential Phase 2/3 registrational trial package to submit to the FDA.

If successful, azer-cel could become the first approved allogeneic CAR T cell therapy for blood cancer. Furthermore, Imugene intends to explore the use of azer-cel in combination with its onCARlytics program for treating solid tumors, potentially expanding its market to the 90% of cancers that are not blood-related.

The Phase 1b azer-cel trial is an open-label, multi-center study ongoing in the US and Australia, targeting DLBCL patients who have relapsed after autologous CAR T therapies. All patients treated so far have shown an acceptable safety profile, with encouraging clinical activity and response durability, particularly in Cohort B.

DLBCL is a fast-growing form of NHL, with approximately 80,500 cases annually in the U.S. alone. The relapse rate for patients treated with autologous CD19 CAR T therapies remains high, underscoring the critical need for new treatments like azer-cel. IL-2, a cytokine that promotes T-cell growth and survival, has been incorporated into the trial to enhance the effectiveness of CAR T cells in targeting and eliminating cancer cells.