Imugene Limited has announced compelling new data from its Phase 1b clinical trial of azer-cel (azercabtagene zapreleucel), an allogeneic off-the-shelf CAR T-cell therapy targeting CD19 in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The updated results show a 75% overall response rate (ORR) with six complete responses (CR) and three partial responses (PR) among 12 patients treated in the trial.
Strong Response Rates in Heavily Pre-treated Population
Since Imugene's February 2025 update, five additional patients have been dosed, resulting in two new complete responses and three partial responses. The complete response rate now stands at 55%, representing a significant achievement in patients who have previously failed at least three lines of therapy, with many having failed four to six lines of treatment, including autologous CAR T therapies.
The first patient in the trial remains cancer-free at 15 months, with additional patients demonstrating durable responses at 2, 5, and 11 months. The duration of response data continues to mature, with further updates expected in the coming months.
"We are very pleased with the continued positive data coming from the azer-cel trial, which further reinforces its potential as a treatment for DLBCL patients who have failed several previous lines of therapy," said Leslie Chong, Managing Director and CEO of Imugene.
Addressing Key Limitations of Current CAR T Therapies
Azer-cel is being developed as a potential allogeneic, off-the-shelf CAR T-cell therapy designed to address key limitations of approved autologous CAR T drugs, including geographical access to treatment centers, manufacturing complexity, and time to receive treatment. For approved autologous CD19 CAR T products, the average time to best response is 2-3 months, with some patients taking up to 6 months to achieve their best response.
The therapy is administered with lymphodepletion and interleukin-2 (IL-2), a cytokine that helps T-cells grow and survive while enhancing the cancer-killing functions of CAR T cells. The safety profile has been manageable and generally well tolerated according to the trial data.
Regulatory Path Forward and Trial Expansion
Based on the updated response rate and maturing durability data, along with FDA Fast Track Designation awarded for DLBCL in March 2025, Imugene will request a Type B (End of Phase 1) Meeting in Q4 2025 with the US FDA to present the data and discuss designs for a pivotal/registrational trial for azer-cel.
The FDA Fast Track Designation is designed to facilitate development and expedite review of drugs that address serious or life-threatening conditions and meet an unmet medical need. Benefits include more frequent FDA meetings, rolling review options, and potential eligibility for Accelerated Approval and Priority Review.
Given the positive results, the trial is expanding to include CAR T-naïve patients with other niche blood cancer indications, including primary central nervous system lymphoma (PCNSL) and other subtypes of B-cell lymphoma such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), and follicular lymphoma (FL).
"This is a high unmet need with potential to expedite and expand the scope of azer-cel," Chong noted.
Addressing Significant Unmet Medical Need
DLBCL is the most common type of non-Hodgkin's lymphoma, with approximately 160,000 global cases per year and approximately 30,000 new cases annually in the U.S. Relapsed/refractory DLBCL represents a high unmet medical need, with approximately 60% of patients treated with approved autologous CD19 CAR T therapies experiencing relapse.
Dr. John Byon, Chief Medical Officer of Imugene, emphasized the clinical significance: "DLBCL remains one of the most aggressive forms of lymphoma, and despite the existing therapies, there are a large number of patients that still face relapse or resistance. We are seeing significant potential from azer-cel to date in its ability to provide a critical step forward for these patients who have relapsed on multiple therapies, offering deep and durable responses with a one-time treatment."
The Phase 1b trial continues to actively enroll patients at ten US sites with up to six sites planned in Australia, following the first Australian patient being dosed in January 2025 at Royal Prince Alfred Hospital in Sydney, resulting in a complete response.
