ZUMA-23 (NCT05605899) is an on-going phase 3 study investigating axicabtagene ciloleucel (axi-cel) CAR T cell therapy as a first-line therapy in patients with high-risk large B-cell lymphoma. touchONCOLOGY caught up with Dr Jason Westin (The University of Texas MD Anderson Cancer Center, Houston, TX, USA) to discuss what previous clinical trials have taught us about axi-cel, what questions remain unanswered, and the aims, rationale and methodology of the ZUMA-23 study. He also touched upon topics to explore for 2023 in the field of haematology.
The abstract entitled ‘PB2319 ZUMA-23: A GLOBAL, PHASE 3, RANDOMIZED CONTROLLED STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE AS FIRST-LINE THERAPY IN PATIENTS WITH HIGH-RISK LARGE B-CELL LYMPHOMA’ was presented at the EHA 2023 Congress, 8–11 and 14–15 June 2023.
- What have previous clinical trials taught us about axi-cel and what questions remain unanswered? (0:16)
- What are the aims, rationale and methodology of the ZUMA-23 study? (1:48)
- What areas in the field of haematology are you most looking forward to exploring in 2023? (3:30)
Disclosures: Jason Westin acts as a consultant for, has received grant/research support from, and is on the advisory board of Abbvie, ADC Therapeutics, AstraZeneca, BMS, Genentech, Genmab, Kite/Gilead, Morphosys, and Novartis.
Support: Interview and filming supported by Touch Medical Media. Interview conducted by Atiya Henry.
Filmed as a highlight of EHA 2023.
Hi. I’m Dr Jason Westin from MD Anderson Cancer Center in Houston, Texas. I am the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas.
What have previous clinical trials taught us about axi-cel and what questions remain unanswered? (0:16)
Previous clinical trials have taught us a lot about CAR T-cell therapy and axi-cel, specifically in the ZUMA-1 trial, was shown to be very effective in patients who had multiply relapsed or refractory large B-cell lymphoma, achieving high response rates, and durable responses in a significant portion of patients. More recently, in the ZUMA-7 clinical trial, axi-cell was compared against platinum chemotherapy and high-dose therapy in autologous transplant, and shown to be superior to the old standard both on event-free survival, and more recently having a superior overall survival, a major finding that we just reported here in 2023 at the ASCO meeting, the New England Journal, and being discussed at IHA as well as at the Lugano meeting. Overall survival is a hard endpoint. It is something that’s hard to argue with having more people living longer with the treatment, and so axi-cel in second line now is emerging as a standard of care option as a result. Questions left to be unanswered include what would happen if we were to evaluate axi-cel in a first line setting in high risk patients with newly diagnosed disease, and thankfully, we have a trial that’s asking that exact question in the ZUMA-23 study, which is randomizing patients with newly diagnosed disease with IPI 4 and 5 to receive either six cycles of R-chemotherapy or axi-cel in the front line setting.
What are the aims, rationale and methodology of the ZUMA-23 study? (1:48)
The ZUMA-23 study is an up and running, as of now, actively accruing, trial as a global Phase 3 study, and the aims of this study are to identify if axi-cel can improve survival outcomes, event-free survival, progression-free survival, overall survival, in comparison with the existing standard of care for R-chemotherapy. Axi-cel has beaten all comers in a third line setting, and in a second line setting, well, let’s go a first line setting and see if it can do it there. So those are the key and secondary endpoints, event-free survival, progression-free, and overall survival, overall response rate. The rationale for it is that ZUMA-12 showed us that axi-cel has a very high overall response rate in patients with high risk disease in the frontline setting, nearly 90% response rate, and nearly an 80% complete response rate. Progression-free survival in ZUMA-12 was 75% in a similar patient population to what’s being targeted in ZUMA-23. So the ZUMA-23 trial has a strong rationale for you asking this question. In terms of methodology, patients are randomized one to one to receive either six cycles of our chemo or to receive effectively two cycles of our chemo as bridging therapy prior to and after manufacturing has started for axi-xel, and then one dose of axi-cel and they’re done. So it’s a one to one randomization, but the treatment arms are quite different, and then patients will be followed, of course, to see which treatment is superior.
What areas in the field of haematology are you most looking forward to exploring in 2023? (3:30)
The areas of research and haematology that I’m most interested in exploring in 2023 include how do we combine and sequence all of the great new targeted therapies that are being developed. We have an absolute explosion of great new weapons in our battle against B-cell lymphoma, including kinase inhibitors, including CAR T-cell therapies, including antibody-drug conjugates, antibodies, and bispecific antibodies, which are rapidly emerging on the scene as a great new weapon. It’s hard to know which patient should receive which of those treatments. And so things I’m most interested in are how do we combine these more successfully, and how do we select which patient is gonna benefit most from which treatment.
Subtitles and transcript are autogenerated
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