ZUMA-22: A phase 3, randomized controlled study of axicabtagene ciloleucel (axi-cel) versus standard-of-care therapy in patients with relapsed or refractory (R/R) follicular lymphoma (FL).

Ian W. Flinn Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN info_outline Ian W. Flinn, Caron Alyce Jacobson, Loretta J. Nastoupil, Franck Morschhauser, Andrew Davies, Christian Buske, Paolo Corradini, Armando López Guillermo, Ran Reshef, Vinod Parameswaran, Alison Sehgal, Michael Timothy Tees, Christine Lui, Wei Xue, Sara Beygi, Nikolay Grechko, Pisita Bolsue, Alessandro Giovanetti, Christina Ann To, Myrna Nahas

Authors Ian W. Flinn Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN info_outline Ian W. Flinn, Caron Alyce Jacobson, Loretta J. Nastoupil, Franck Morschhauser, Andrew Davies, Christian Buske, Paolo Corradini, Armando López Guillermo, Ran Reshef, Vinod Parameswaran, Alison Sehgal, Michael Timothy Tees, Christine Lui, Wei Xue, Sara Beygi, Nikolay Grechko, Pisita Bolsue, Alessandro Giovanetti, Christina Ann To, Myrna Nahas Organizations Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, Dana-Farber Cancer Institute, Boston, MA, MD Anderson Cancer Center, Houston, TX, University of Lille, Centre Hospitalier Universitaire, Lille, France, Southampton Experimental Cancer Medicines Centre, University of Southampton, Southampton, United Kingdom, Institute of Experimental Cancer Research, Comprehensive Cancer Center Ulm, University Hospital Ulm, Ulm, Germany, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, University of Barcelona, Barcelona, Spain, Columbia University Medical Center, New York, NY, Avera Medical Group Hematology, Transplant, and Cellular Therapy, Sioux Falls, SD, University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, Colorado Blood Cancer Institute, Denver, CO, Kite, a Gilead Company, Santa Monica, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Kite, a Gilead Company Background: Patients with R/R FL experience progressively shorter remissions with each successive line of therapy, and the disease is largely considered incurable (Batlevi et al. Blood Cancer J. 2020). Patients who relapsed < 24 months after initiating first-line chemoimmunotherapy (POD24) have inferior overall survival compared with those who did not experience POD24 (Casulo, Barr. Blood. 2019). However, outcomes of R/R FL have improved with the introduction of novel options including chimeric antigen receptor (CAR) T-cell therapy, a highly effective approach with potential to change the treatment paradigm (Jacobson et al. Lancet Oncol. 2021; Freedman, Jacobson. Am J Hematol. 2020). Axi-cel, an autologous anti-CD19 CAR T-cell therapy, is approved for the treatment of R/R FL. In ZUMA-5, a single-arm, Phase 2 study of axi-cel in indolent non-Hodgkin lymphoma, patients with FL (n = 127) had a median progression-free survival of 40.2 months and median overall survival not yet reached after median follow-up of 41.7 months, with manageable long-term safety (Neelapu et al. ASH 2022. Abstract 4660). In ZUMA-5, POD24 did not adversely affect progression-free survival or overall survival. ZUMA-22 is a Phase 3, open-label, multicenter, randomized controlled trial that will evaluate the efficacy and safety of axi-cel compared with standard-of-care therapy in patients with R/R FL. Methods: The study will enroll approximately 230 adult patients with FL (Grades 1-3a) who have either had 1 prior line of therapy and experienced POD24 or had ≥2 prior lines of systemic therapy. Patients will be randomized 1:1 to receive axi-cel or standard-of-care therapy. Patients in the standard-of-care therapy arm will receive investigator’s choice of either rituximab + lenalidomide, rituximab + CHOP, or rituximab + bendamustine. Patients in the axi-cel arm will undergo leukapheresis, followed by optional bridging therapy, lymphodepleting chemotherapy (fludarabine/cyclophosphamide), and a single axi-cel infusion (2×10 6 CAR T cells/kg). The primary endpoint is progression-free survival by blinded central assessment per Lugano classification (Cheson et al. J Clin Oncol. 2014). Secondary endpoints include complete and overall response rates, duration of response, overall survival, event-free survival, time to next treatment, safety, and quality-of-life assessments. Additional key inclusion criteria are ECOG 0-1, presence of ≥1 measurable lesion, and adequate bone marrow and organ function. Those with HIV or hepatitis B or C and an undetectable viral load are eligible. Key exclusion criteria are a history of large B-cell lymphoma or transformed FL, and FL Grade 3b. The study is currently open and actively accruing patients at several sites globally (NCT05371093). Clinical trial information: NCT05371093.

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