Optimizing R/R DLBCL Treatment: Azer-Cel Shows Sustained Responses

Updated data from a phase 1b clinical trial (NCT03666000) evaluating azercabtagene zapreleucel (azer-cel; PBCAR0191), an investigational allogeneic, off-the-shelf chimeric antigen receptor (CAR) T-cell therapy, in combination with lymphodepletion and interleukin 2 (IL-2), demonstrated continued promising activity in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).¹

As of the latest data release, 6 out of 11 evaluable patients (55%) achieved a complete response (CR), defined as the disappearance of all signs of cancer. This builds upon preliminary data from February 2025, which reported a CR in 4 out of 7 patients. The best overall response rate (ORR) has reached 75% (n = 9/12), including 3 patients who achieved a partial response, defined as cancer reduction by at least 50%. The duration of response continues to mature, with some responses ongoing for over 450 days. These results compare favorably to approved autologous CD19-directed CAR T products, where the average time to best response is typically 2 to 3 months, with some patients taking up to 6 months.

DLBCL is an aggressive and rapidly progressing form of non-Hodgkin lymphoma (NHL), representing the most common type of NHL, with approximately 160,000 global cases annually and 30,000 new cases in the US per year. Despite existing therapies, a significant proportion of patients with relapsed/refractory DLBCL experience disease progression, highlighting a substantial unmet medical need. Current approved autologous CD19 CAR T therapies see approximately 60% of patients relapse.

Azer-cel is being developed as a potential alternative to approved autologous CAR T-cell therapies, addressing several limitations, including geographical access to specialized treatment centers, complexities in manufacturing, and the extended time required for patient-specific product generation. The allogeneic nature of azer-cel aims to streamline access and delivery of CAR T-cell therapy.

Based on the evolving response and durability data and having received FDA fast track designation for DLBCL in March 2025, Imugene Limited plans to request an end-of-phase 1 meeting with the FDA in the fourth quarter of 2025. This meeting will facilitate discussions regarding the clinical data and potential designs for a pivotal/registrational trial for azer-cel. The FDA fast track designation is intended to expedite the development and review of drugs for serious or life-threatening conditions that address unmet medical needs. This designation offers benefits such as more frequent FDA meetings, potential for rolling review of regulatory submissions, and eligibility for accelerated approval and priority review if relevant criteria are met.

"We are very pleased with the continued positive data coming from the azer-cel trial, which further reinforces its potential as a treatment for [patients with] DLBCL who have failed several previous lines of therapy," stated Leslie Chong, managing director and chief executive officer of Imugene, in a press release. "The data also significantly improves our position from both a regulatory and commercial standpoint, and we look forward to expanding on these discussions with the FDA."

The phase 1b azer-cel trial is an ongoing, open-label, multicenter study enrolling patients across 18 US sites, with up to 6 Australian sites planned.² The first Australian patient was dosed in January 2025 at Royal Prince Alfred Hospital in Sydney, also resulting in a CR.¹

The treatment regimen includes lymphodepletion and IL-2, a cytokine that promotes the growth and survival of T cells and enhances their cancer-killing functions, making CAR T cells more effective at targeting and eliminating cancer cells. Patients must have had at least 3 prior lines of therapy, with many patients failing 4 to 6 lines of therapy, including autologous CAR T-cell therapy. The safety profile of azer-cel to date has been reported as manageable and generally well-tolerated.

Beyond DLBCL, the trial has recently expanded to include CAR T-naive patients with other niche blood cancer indications, including primary central nervous system lymphoma (PCNSL) and other subtypes of B-cell lymphoma. These include chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone lymphoma, Waldenström macroglobulinemia, and follicular lymphoma. This expansion reflects the encouraging activity observed with azer-cel and aims to address high unmet needs in these additional patient populations. PCNSL, for instance, is a rare and aggressive form of NHL with limited approved treatment options, with approximately 1500 to 1800 new cases annually in the US. There are currently no approved CAR T-cell products for PCNSL.

REFERENCES:

1. Imugene announces outstanding response rates from the phase 1b trial of the azer-cel allogeneic CAR T in 3L+ DLBCL. News release. Imugene Limited. July 14, 2024. Accessed July 14, 2025. https://tinyurl.com/yc5adbsr

2. 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 July 14, 2025. https://clinicaltrials.gov/study/NCT03666000