Imugene Ltd (ASX:IMU, OTC:IUGNF) has reported encouraging early efficacy data from the CAR T-naïve portion of its ongoing Phase 1b trial of azer-cel (azercabtagene zapreleucel) — an off-the-shelf, allogeneic CD19 CAR T-cell therapy being tested across multiple B-cell lymphoma types.
Of six evaluable patients with no prior CAR T treatment, five (83%) achieved an overall response, including three (50%) complete responses. Results from a sixth patient are pending. Ten patients have been treated so far in this cohort, spanning several rare and difficult-to-treat lymphoma subtypes such as Waldenström macroglobulinemia, marginal zone lymphoma and primary CNS lymphoma — areas where no CAR T therapies are currently approved.
Fast-moving enrolment and strong demand
Imugene said enrolment for the CAR T-naïve cohort is proceeding significantly faster than in the earlier CAR T-relapsed diffuse large B-cell lymphoma (DLBCL) group, highlighting strong clinical demand for an allogeneic option. The company described azer-cel’s safety profile as manageable and consistent with previous data in relapsed DLBCL.
“We are encouraged by these early signals of efficacy in the CAR T-naïve population, with at least five of the first six evaluable patients responding to treatment,” said Imugene chief executive officer Leslie Chong.
“As best responses can be seen up to 90 days or more after treatment, we look forward to further data on the depth and durability of these outcomes,” she added. “Enrolment in this portion of the trial is proceeding at a remarkable pace, positioning us to explore an expedited development pathway for azer-cel.”
Next regulatory milestone
Imugene will hold an FDA Type C meeting in November to discuss pivotal-study design options for azer-cel in the CAR T-relapsed DLBCL setting, while also expanding the CAR T-naïve program to support potential registration across additional indications, including rare lymphomas.
The company’s previously reported results from the CAR T-relapsed DLBCL cohort showed an 81% overall response rate, with several patients remaining in durable remission beyond a year despite having failed an average of three prior therapies — including autologous CAR T.
Read more: Imugene lifts response rate to 81% in azer-cel CAR T Phase 1b trial
Together, the two datasets strengthen the case for azer-cel as a differentiated allogeneic CAR T candidate for both relapsed and treatment-naïve patients, Imugene said.
About the azer-cel trial
The ongoing multi-centre, open-label Phase 1b trial is evaluating azer-cel in the US and Australia across a range of CD19-positive B-cell malignancies, including DLBCL, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone lymphoma, Waldenström macroglobulinemia and primary CNS lymphoma.
Treatment combines azer-cel with lymphodepletion and interleukin-2, and has so far shown meaningful clinical activity and tolerability.