Aine Hurley, MD, Malaghan Institute of Medical Research, Wellington, New Zealand, discusses the ENABLE-2 clinical trial which will evaluate the efficacy and safety of WZTL-002, a third-generation anti-CD19 CAR T-cell therapy, among patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) who have received 1 or 2 prior lines of therapy.

Dr Hurley stated, “This is an aggressive disease and response rates to salvage chemotherapy in a refractory setting are poor. Hence, we need to further establish the role of CAR T-cell therapy in these patients.”

Transcript:

Hi there. My name is Aine Hurley. I'm a clinical research CAR-T fellow at the Malaghan Institute of Medical Research in New Zealand, and I've had the privilege to present our trial, ENABLE-2 trial and progress at ASCO 2025.

The phase 2 trial has begun in July 2024 on the basis of a phase 1 trial that was conducted in New Zealand in Wellington from 2019. We are looking at the use of third generation, anti-CD19 CAR T-cells in the treatment of relapsed and refractory B-cell lymphoma.

The trial that was done from 2019 to 2024 has some results that now show complete response in 52% of patients at 3 months with very low toxicity rates. Cytokine release syndrome at 57% and immune-effector cell associated neurotoxicity syndrome (ICANS) at 3%. These toxicities appears low in comparison to axicabtagene ciloleucel, which is the main comparator as seen in the ZUMA studies.

With our phase 2 trial we aim to include 80 participants over 2 years and we're looking at treating relapsed and refractory lymphomas. Eligibility criteria are patients aged 18 to 75 with a performance status of 0 to 1 and histologically confirmed high grade B-cell lymphomas, which can be transformed from follicular or marginal zone lymphomas as well. Patients must have PET-avid disease at the time of screening, and patients are allowed to have bridging therapy between pheresis and administration of CAR T-cells.

This trial is unique in that we are offering outpatient monitoring and management after the CAR T-cell treatment, with patients advised to be within 30 minutes of the center or living nearby at a cancer accommodation close to the study site. Patients attend daily for CRS and ICE assessments to assess if there are any immune-effector cell toxicities arising as a result of the treatment and this continues for 14 days.

At 1 month, patients are assessed with a PET CT scan and again at 3 months to assess for complete response. We are hoping that the efficacy results in our phase 2 trial improve those seen in phase 1 as we are treating patients in the earlier line of treatment. Patients must be refractory to frontline chemo immunotherapy, which usually consists of at least 6 cycles of an anti-CD20 monoclonal antibody and cytotoxic chemotherapy or patients who had an early relapse within 12 months. We are also treating patients who are refractory or have inadequate response to salvage chemotherapy to proceed with an autologous stem cell transplant or indeed patients who relapse after an autologous stem cell transplant.

With the trial our co-primary end points are of course efficacy of the CAR T-cell as measured by complete response rates at 3 months after treatment, and ICANS incidence is a key safety measure. Secondary end points include other safety data such as CRS and ICANS incidents and we hope to have results from our phase 2 trial in 2026 to 2027. All patients are enrolled in a long-term extension, follow-up to monitor for secondary malignancies and other late effects of CAR T-cell treatment.

We hope to demonstrate efficacy of our CAR T-cell product, which is called WZTL-002. It is a third generation, anti-CD19 CAR T-cell as opposed to axicabtagene ciloleucel, which is second generation. The addition of extra costimulatory domain called toll-like receptor 2 makes a third generation and this is possibly thought to modify some of the cytokine effects of the CAR T and perhaps lower the immune-effector cell toxicities, although this is yet to be formally confirmed.

With our CAR T-cell treatment, we are hoping to treat patients who relapsed and refractory in the unique New Zealand setting where there are limited novel therapies available for refractory and relapsed diffuse large B-cell lymphoma. The eventual aim is to hope that CAR T-cell therapy will be improved and funded for patients in New Zealand.

This is an aggressive disease and response rates to salvage chemotherapy in a refractory setting are poor. Hence, we need to further establish the role of CAR T-cell therapy in these patients.

Source:

Hurley A, George P, Giunti G, et al. A phase 2 trial to evaluate the efficacy and safety of WZTL-002, a third-generation anti-CD19 CAR T-cell therapy, in patients with relapsed or refractory large B-cell lymphoma (ENABLE-2). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract TPS7084.