Phase 1 Study of KITE-222, an Autologous CLL-1–Directed CAR T-cell Therapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy has been a breakthrough in many hematologic malignancies, but success in relapsed/refractory (R/R) acute myeloid leukemia (AML) has been limited due to underwhelming response rates and high on-target/off-tumor toxicity. This phase 1 dose-escalation trial evaluated the safety and efficacy of KITE-222, an autologous CAR T-cell therapy that recognizes C-type lectin-like molecule 1 (CLL-1), predominantly expressed on myeloid cells but absent on normal hematopoietic stem cells and other tissues. PATIENTS AND METHODS: Patients with R/R AML (≥50 kg) received a single intravenous infusion of 3 × 107 (cohort 1), 1 × 108 (cohort 2), or 3 × 108 (cohort 3) KITE-222 CAR+ T cells. The primary endpoint was the incidence of dose-limiting toxicities (DLT). Key secondary endpoints included overall remission rate, incidence of adverse events (AE), and pharmacokinetics/pharmacodynamics. RESULTS: Twelve patients received KITE-222. One patient in cohort 3, who was the only patient to receive two courses of lymphodepleting chemotherapy, experienced a DLT (prolonged grade 4 neutropenia/thrombocytopenia) but achieved a best response of morphologic leukemia-free state on day 14 following infusion (confirmed on day 44). All patients experienced grade ≥3 AEs, none had grade ≥3 cytokine release syndrome, and one had grade ≥3 immune effector cell-associated neurotoxicity syndrome. Clinically meaningful responses were lacking across dose levels despite detectable CAR T-cell expansion. Although two of five cohort 3 patients with clear expansion had near-complete depletion of CLL-1+ bone marrow blasts after infusion, CLL-1- blasts persisted, and reductions in total blasts were not observed. CONCLUSIONS: Despite successful manufacturing and acceptable safety, KITE-222 lacked preliminary efficacy, warranting future studies that address CLL-1 heterogeneity and focus on improving in vivo expansion and antitumor activity.
Source: Clinical Cancer Research
Institutions: The University of Texas MD Anderson Cancer Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Washington University in St. Louis, Cleveland Clinic, Stanford Medicine, Stanford University, Centre National de la Recherche Scientifique, Inserm, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Moffitt Cancer Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7150917102