Imugene reports 100% response rate in CLL/SLL and 80% in MZL from azer-cel Phase 1b study
Imugene Limited (ASX: IMU) has reported encouraging early Imugene azer-cel response rates from its ongoing Phase 1b basket study, with 100% overall response rate (ORR) achieved in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients and 80% ORR in marginal zone lymphoma (MZL) patients. The data comes from the CAR T-naïve cohort evaluating azer-cel, an off-the-shelf allogeneic CAR T cell therapy targeting CD19 in advanced B-cell malignancies.
Patients enrolled in the study had received multiple prior lines of therapy, with a median of ≥3 prior treatments for CLL/SLL and ≥2 for MZL. Enrolment in the CAR T-naïve cohort is progressing faster than in the earlier CAR T-relapsed DLBCL cohort, reflecting strong clinical demand. The company is actively enrolling patients across ten US sites and five Australian sites.
In CLL/SLL, the 100% ORR comprised four partial responses (PR) out of four evaluable patients. According to US FDA guidance, partial responses in CLL/SLL have historically been sufficient to support regulatory approvals, as complete responses are uncommon in this indication. In MZL, the 80% ORR included three complete responses (CR) and one partial response out of five evaluable patients, demonstrating depth of activity beyond disease stabilisation.
| Indication | ORR | Complete Responses | Partial Responses | Prior Lines (Median) |
|---|---|---|---|---|
| CLL/SLL | 100% | 0 | 4/4 | ≥3 |
| MZL | 80% | 3/5 | 1/5 | ≥2 |
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Understanding overall response rates in blood cancer trials
Overall Response Rate (ORR) refers to the proportion of patients whose cancer shrinks or disappears after treatment. It serves as a primary efficacy measure regulators use to assess cancer therapies in clinical trials. In blood cancer studies, responses are categorised into distinct classifications based on disease burden reduction.
The key response categories include:
- Overall Response Rate (ORR): The combined percentage of patients achieving either complete or partial response.
- Complete Response (CR): All measurable or visible signs of cancer are no longer detectable following treatment.
- Partial Response (PR): Significant reduction in tumour size (typically at least 50%) or disease burden, but not complete disappearance of the disease.
- Progressive Disease (PD): Cancer has grown or spread despite treatment.
In CLL/SLL specifically, complete responses are rare and partial responses have been sufficient to support regulatory approvals. This makes the 100% ORR comprising four partial responses particularly meaningful from a regulatory pathway perspective.
Azer-cel’s allogeneic (off-the-shelf) approach differs from autologous CAR T therapies in a fundamental way. Autologous therapies require manufacturing from each patient’s own cells, creating production delays and logistical challenges. Allogeneic therapies are pre-manufactured from donor cells, enabling immediate availability and potentially reducing costs.
Basket trial design opens multiple registrational pathways
The azer-cel Phase 1b CAR T-naïve cohort is structured as a multi-indication basket trial, a capital-efficient development strategy that evaluates the therapy across multiple B-cell malignancies simultaneously. This design allows Imugene to prioritise indications demonstrating the strongest clinical activity whilst maintaining flexibility to discontinue pursuit of others.
The basket study currently includes several B-cell lymphoma subtypes, each with specific prior therapy requirements:
- Primary Central Nervous System Lymphoma (PCNSL): Patients with ≥1 prior line of therapy containing high-dose methotrexate.
- Diffuse Large B-Cell Lymphoma (DLBCL): Patients with ≥1 prior line of therapy including anti-CD20 and anthracycline.
- Waldenström’s Macroglobulinemia (WM): Patients with ≥2 prior lines of therapy including anti-CD20 chemoimmunotherapy.
- Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL): Patients with prior BTK inhibitor (BTKi) and BCL2i, or prior BTKi with high-risk features.
- Marginal Zone Lymphoma (MZL): Patients with ≥2 prior lines of therapy including anti-CD20 chemoimmunotherapy.
Clinical data across these indications continues to mature. Management intends to prioritise those indications demonstrating the strongest clinical activity, whilst certain other indications may not be pursued further. Durability of response, depth of response, and safety profiles continue to develop as patient enrolment progresses.
The basket design provides multiple shots on goal across different B-cell malignancies with significant unmet need, potentially supporting a fast-to-market strategy if one or more indications demonstrate compelling activity.
BTK inhibitor combination arm expands commercial opportunity
Imugene has amended the Phase 1b protocol to evaluate azer-cel in combination with a BTK inhibitor (BTKi) and to include patients with mantle cell lymphoma (MCL). The combination arm will enrol patients who have previously failed BTK inhibitor therapy to evaluate safety and preliminary efficacy, including response rates.
BTKis are approved drugs used to treat B-cell cancers, primarily CLL. They have largely replaced traditional chemotherapy as the standard first-line treatment for CLL. The global BTK inhibitor market has become a substantial sector in oncology, with annual sales reaching approximately $12.1 billion in 2025, shared between J&J/AbbVie, BeiGene, AstraZeneca, and Eli Lilly.
Targeting patients who have failed prior BTK inhibitor therapy positions azer-cel in a growing population with limited treatment options. As BTKis become increasingly established as standard therapy, patients who relapse or become resistant to these agents represent a meaningful addressable market. Combination strategies may strengthen competitive positioning whilst potentially improving patient outcomes in this difficult-to-treat population.
CEO commentary on clinical progress
Chief Executive Officer Leslie Chong highlighted the breadth of activity emerging across multiple lymphoma subtypes and the strategic value of the BTKi combination programme.
Leslie Chong, Chief Executive Officer
“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. The addition of the BTK inhibitor combination arm represents a meaningful opportunity to expand the clinical scope of the programme, particularly for advanced patients who have failed prior BTK inhibitor therapy. We believe this strategy may further strengthen the positioning of azer-cel whilst aiming to improve outcomes for patients with limited treatment options.”
Significant unmet need in relapsed/refractory B-cell malignancies
Diffuse Large B-Cell Lymphoma (DLBCL) represents the most common type of non-Hodgkin’s lymphoma, with approximately 160,000 global cases per year and approximately 30,000 new cases annually in the US. Relapsed/refractory DLBCL presents a high unmet medical need, with approximately 60% of patients treated with approved autologous CD19 CAR T therapies subsequently relapsing.
The substantial relapse rate following autologous CAR T treatment creates a meaningful addressable market for alternative therapeutic approaches. Other B-cell lymphoma subtypes similarly face treatment challenges. CLL/SLL represents the most common slow-growing leukaemia that can become resistant to therapy. Relapsed/refractory mantle cell lymphoma (MCL), MZL, WM, and follicular lymphoma (FL) each present distinct clinical challenges.
Whilst several targeted therapies and monoclonal antibodies are available for these B-cell malignancies, relapsed or refractory disease remains an ongoing challenge. The multiple B-cell malignancy subtypes with unmet need expand the total addressable opportunity for therapies demonstrating broad activity across indications.
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Next steps and what to watch
Enrolment is ongoing across 15 sites (10 in the US and 5 in Australia), with the CAR T-naïve cohort progressing faster than the earlier CAR T-relapsed DLBCL cohort. This accelerated enrolment reflects strong clinical investigator interest in the allogeneic approach and potential application across multiple B-cell malignancies.
Key upcoming milestones and developments to monitor include:
- Additional response data as more patients become evaluable across the basket study indications.
- Durability data as follow-up periods extend and long-term response rates mature.
- Safety profile characterisation as patient numbers increase and exposure duration lengthens.
- Potential indication prioritisation announcements as management focuses resources on indications demonstrating strongest signals.
- Initial data from the BTKi combination arm evaluating safety and preliminary efficacy in BTKi-failed patients.
- Enrolment updates across the expanding site network and patient cohorts.
Further updates will be provided as additional patients become evaluable and data matures across the multiple indications under evaluation.
Ready to Learn More About Imugene’s Azer-Cel Programme?
Imugene’s off-the-shelf CAR T therapy is demonstrating promising early activity across multiple B-cell malignancies, with 100% response rates in CLL/SLL and strong signals in MZL. The basket trial design and BTK inhibitor combination arm position azer-cel to address substantial unmet need in relapsed/refractory blood cancers.
To explore Imugene’s full clinical pipeline, upcoming milestones, and investment case, visit the Imugene investor centre. Stay informed on response durability, safety data, and potential regulatory pathways as this Phase 1b study continues to mature.