Highlights:

IMU reports 6 complete and 3 partial responses in Phase 1b DLBCL trial.

IMU's first patient remains cancer-free at 15 months; durability data continues to mature.

FDA meeting planned in Q4 2025 to discuss pivotal trial for azer-cel.

Imugene Limited (ASX:IMU), a clinical-stage immuno-oncology company headquartered in Sydney, has released updated results from its ongoing Phase 1b clinical trial of azer-cel (azercabtagene zapreleucel) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The trial is investigating azer-cel, an allogeneic (off-the-shelf) CD19-targeting CAR T-cell therapy designed to overcome some limitations of autologous CAR T treatments.

As of the July 2025 update, the study has dosed five additional patients since the previous announcement in February, bringing the total number of treated patients to 12. Of these, six have achieved complete responses (CRs) and three have partial responses (PRs), translating to a 75% overall response rate (ORR). The complete response rate now stands at 55%.

The first patient enrolled remains cancer-free at 15 months post-treatment. Additional patients are showing sustained responses at intervals of 2, 5, and 11 months, with durability data still being collected. All participants in the trial had received at least three prior lines of therapy, with many having undergone four to six previous treatments, including autologous CAR T-cell therapy.

The ongoing Phase 1b study combines azer-cel with interleukin-2 (IL-2), a cytokine known to support T-cell proliferation and survival. Azer-cel is being developed to address logistical and clinical challenges associated with autologous CAR T-cell therapies, such as delays in treatment, manufacturing complexity, and limited access to specialised facilities.

Based on the latest data, Imugene plans to request a Type B (End of Phase 1) meeting with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2025. The meeting will focus on discussing the clinical data to date and outlining the design of a potential registrational trial for azer-cel in DLBCL. The product received FDA Fast Track Designation in March 2025.

In addition to patients previously treated with CAR T-cell therapy, the study has recently expanded to include individuals with CAR T-naïve subtypes of B-cell lymphoma. These subtypes include primary central nervous system lymphoma (PCNSL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), and follicular lymphoma (FL). These cancers are associated with limited treatment options following relapse, and currently, no CAR T therapies are approved for PCNSL.

DLBCL is the most common type of non-Hodgkin lymphoma (NHL), accounting for an estimated 160,000 global cases annually, including approximately 30,000 new diagnoses per year in the United States. Patients with relapsed or refractory DLBCL face limited treatment options, with nearly 60% of those receiving existing autologous CAR T therapies eventually relapsing.

PCNSL, one of the trial’s expanded indications, is a rare and aggressive subtype of NHL affecting the central nervous system. With only 1,500 to 1,800 new U.S. cases annually, this disease represents a significant unmet need due to the absence of approved CAR T therapies. Other B-cell lymphoma subtypes included in the expanded cohort also present ongoing clinical challenges, as many patients experience relapse despite multiple available targeted therapies. IL-2 plays a supporting role in the trial by enhancing CAR T-cell activity. It helps T cells persist longer in the body and improves their ability to target cancer cells. The safety profile of azer-cel combined with lymphodepletion and IL-2 has been described as manageable to date.

Imugene’s trial is being conducted at ten clinical sites in the United States and is expanding to six sites in Australia, with the first Australian patient enrolled earlier this year at Royal Prince Alfred Hospital in Sydney. That patient also achieved a complete response. An additional update on the trial’s progress and patient outcomes is expected in the coming months.