ZUMA-8: A phase 1/2 multicenter study evaluating KTE-X19 in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

Abstract

TPS7566 Background: Despite treatment advances, CLL is largely incurable. First-line targeted therapy with ibrutinib mostly produces durable remissions, but high-risk disease or many prior therapies increases relapse risk (Ghia P, et al. Haematologica. 2014). Relapse after ibrutinib is associated with a poor outcome (Maddocks KJ, et al. JAMA Oncol. 2015). Allogeneic stem cell transplantation potentially offers long-term remissions but has a high risk of morbidity/mortality (Shustik C, et al. Ann Hematol. 2017). Autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) with a CD28 costimulatory domain may be efficacious against CLL (Kochenderfer JN, et al. Blood. 2012). KTE-X19 is an autologous anti-CD19 CAR T cell therapy under investigation for R/R hematologic malignancies and may offer longer durable remissions with manageable safety in pts with R/R CLL. ZUMA-8 is a Phase 1/2 multicenter study for pts with R/R CLL. Methods: Adult pts must have R/R CLL with ≥ 2 prior treatment regimens, disease progression on ibrutinib, ECOG 0-1, and adequate organ function. Phase 1 will enroll 12-18 pts to assess dose-limiting toxicities (DLTs) with a 6 + 3 dose escalation/de-escalation design; 30 more pts may be enrolled to further assess safety. Phase 2 will enroll ≈60 pts to evaluate efficacy and safety. Pts will undergo leukapheresis followed by optional bridging therapy. Cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) conditioning chemotherapy will be given on Days -5, -4 and -3. KTE-X19 will be given on Day 0 at 0.5, 1 or 2 × 106 KTE-X19 cells/kg. The primary endpoint is incidence of DLTs for Phase 1 and independent review committee-assessed objective response rate (ORR) per iwCLL 2018 criteria for Phase 2. Secondary endpoints include complete remission (CR) rate, investigator-assessed ORR, minimal residual disease (MRD) negativity rate, MRD-negative CR rate, duration of response, progression-free survival, overall survival, safety, and patient-reported outcomes (Phase 2). Serum cytokine and blood KTE-X19 cell levels over time and level of anti-KTE-X19 antibodies are exploratory endpoints. Accrual is ongoing. Clinical trial information: NCT03624036.