Imugene Ltd (ASX:IMU, OTC:IUGNF) has won crucial backing from the US Food and Drug Administration (FDA), with written minutes from a recent Type C meeting confirming support to advance its off-the-shelf CAR T candidate azercabtagene zapreleucel (azer-cel) into a registrational Phase 3 study.
The meeting, held on November 21, 2025, focused on the proposed pathway to registration for azer-cel in diffuse large B cell lymphoma (DLBCL). The FDA endorsed Imugene’s planned regimen for the pivotal program, which combines augmented lymphodepletion, a fixed dose of 500 million azer-cel cells and 14 days of low-dose subcutaneous interleukin-2 (IL-2).
According to Imugene, the minutes provide “clear alignment” across key elements of the late-stage strategy, including study design, patient population, endpoints and Chemistry Manufacturing Controls (CMC) expectations.
“The alignment across dosing regimen, patient population selection, accelerated approval end point strategy and CMC readiness gives us confidence as we continue to design our pivotal study plans,” Imugene CEO Leslie Chong said. “Combined with our growing clinical data set, we believe azer-cel is well positioned to address high-need patient populations.”
High-need lymphoma setting targeted
The FDA has accepted 3rd line and later DLBCL — including patients who have relapsed after autologous CD19 CAR T therapy — as an appropriate registrational population.
This represents a high-need group where treatment choices are limited and real-world outcomes remain poor, with a substantial proportion of patients progressing after currently approved autologous CAR T products.
The agency also confirmed it would support a single randomised pivotal trial using Overall Response Rate (ORR) and durability of response as the basis for accelerated approval, with Progression Free Survival (PFS) to underpin full approval. The control arm is expected to include several investigator-choice therapies, reflecting current standard practice in this setting.
Imugene said the FDA provided routine statistical guidance that will be incorporated into the final protocol and analysis plan.
Clinical profile continues to build
Clinical activity for azer-cel continues to strengthen across both CAR T-relapsed and CAR T-naïve patient groups.
Updated data from the ongoing Phase 1b trial now show an ORR of 82% in CAR T-relapsed DLBCL and an 83% ORR in CAR T-naïve niche indications across multiple CD19-positive cancers. Durability of response is still maturing, with additional patients maintaining meaningful, ongoing responses.
The Phase 1b study is an open-label, multi-centre trial in the US and Australia that initially enrolled CAR T-relapsed DLBCL patients and has since expanded to include CAR T-naïve patients with a broader range of non-Hodgkin lymphoma subtypes. These include primary central nervous system lymphoma (PCNSL), chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma, Waldenström macroglobulinaemia and follicular lymphoma.
Imugene reports that the combination of azer-cel, lymphodepletion and IL-2 is demonstrating promising anti-tumour activity with a manageable and generally well-tolerated safety profile.
CMC readiness and next steps
On the CMC front, the FDA agreed that Imugene’s manufacturing and quality program is suitable to support initiation of a registrational trial, requesting only standard late-stage refinements to certain analytical methods.
The company plans to compile the FDA’s written minutes and incorporate the guidance into its pivotal study protocol, operational planning and broader clinical program strategy. Further meetings with the agency are anticipated as Imugene refines the pivotal program and statistical analysis plan.
In parallel, rapid enrolment into the CAR T-naïve niche cohort of the Phase 1b trial may open up additional registrational opportunities in other CD19-positive indications, including areas such as PCNSL where no CAR T products are currently approved.
Imugene says it will provide further updates as the azer-cel program progresses through late-stage development and its potential registration pathway becomes more clearly defined.