Clinical-stage immuno-oncology company Imugene Ltd (ASX:IMU, OTC:IUGNF, FRA:ILA) has reported encouraging early response rates from the CAR T-naïve cohort of its ongoing Phase 1b trial evaluating azer-cel, an off-the-shelf cell therapy being tested across several advanced B-cell cancers.
Early data from the study showed a 100% overall response rate (ORR) in patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma (CLL/SLL), while patients with marginal zone lymphoma (MZL) recorded an 80% ORR, including several complete responses.
The results come from a subset of patients treated in the multi-indication basket trial, which is designed to test azer-cel across multiple lymphoma types with significant unmet medical need.
Early activity seen across lymphoma subtypes
In the CLL/SLL group, all four evaluable patients achieved partial responses after receiving a median of at least three prior lines of therapy.
While complete responses are uncommon in this disease setting, partial responses have previously been sufficient to support regulatory approvals for treatments in CLL/SLL.
In the marginal zone lymphoma cohort, four out of five patients responded to treatment. The group included three complete responses and one partial response, producing an overall response rate of 80%.
Patients in this cohort had previously received a median of at least two lines of therapy, including anti-CD20 chemoimmunotherapy.
Imugene said the early signals highlight potential activity for azer-cel across multiple lymphoma subtypes as the dataset continues to expand.
Basket trial designed to identify strongest indications
The Phase 1b CAR T-naïve cohort is structured as a basket study, allowing the company to test the therapy across several B-cell malignancies and focus development on the indications where it shows the most promising activity.
Current indications being evaluated include:
- Primary central nervous system lymphoma (PCNSL)
- Diffuse large B-cell lymphoma (DLBCL)
- Waldenström’s macroglobulinemia (WM)
- Chronic lymphocytic leukaemia / small lymphocytic lymphoma (CLL/SLL)
- Marginal zone lymphoma (MZL)
Imugene said the basket approach could support a faster and more capital-efficient path to potential regulatory approval by prioritising the diseases where the therapy performs best.
Clinical data across these indications is continuing to mature, and the company may narrow the program to focus on those delivering the strongest clinical activity.
Trial enrolment gaining momentum
The company also noted that enrolment in the CAR T-naïve expansion cohort is progressing more quickly than in the earlier cohort of patients whose disease had relapsed after prior CAR T therapy.
According to Imugene, the faster enrolment reflects growing clinical interest in allogeneic, or “off-the-shelf,” CAR T approaches, which are designed to be manufactured in advance rather than individually for each patient.
The trial is currently enrolling patients at 10 clinical sites in the United States and five in Australia, with further updates expected as additional patients become evaluable and follow-up data matures.
Researchers are continuing to assess durability of response, depth of response and safety as the study progresses.
Combination strategy expands program scope
Imugene has also amended the Phase 1b protocol to evaluate azer-cel in combination with Bruton tyrosine kinase inhibitors (BTK inhibitors), a widely used class of drugs for B-cell cancers.
The combination arm will enrol patients who have previously failed BTK inhibitor therapy, allowing investigators to assess safety and early signs of efficacy in this difficult-to-treat population.
The amendment will also allow the trial to include patients with mantle cell lymphoma, expanding the potential reach of the program.
“We are encouraged to see activity emerging across multiple lymphoma subtypes within the CAR T-naïve cohort, which highlights the potential breadth of azer-cel in areas of significant unmet medical need,” Imugene CEO Leslie Chong said.
“The addition of the BTK inhibitor combination arm represents a meaningful opportunity to expand the clinical scope of the program, particularly for advanced patients who have failed prior BTK inhibitor therapy,” she added. “We believe this strategy may further strengthen the positioning of azer-cel while aiming to improve outcomes for patients with limited treatment options.”
Azer-cel targets the CD19 protein expressed on B-cell cancers and forms part of Imugene’s broader pipeline of immunotherapies designed to activate the immune system against tumours.