Phase I study of CN201, a novel CD3xCD19 IgG4 bispecific antibody, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.

6505 Background: Patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) still need more and better treatment options. CN201 is a novel CD19-targeting T-cell-engaging IgG4 bispecific antibody. This phase I study is to investigate the safety, tolerability and preliminary efficacy of CN201 in B-ALL (ClinicalTrials.gov identifier: NCT05579132). The data from the dose escalation and expansion of the ongoing study is presented. Methods: The study is enrolling patients with B-ALL who are refractory to primary induction therapy or to salvage therapy, or relapse. Patients with Philadelphia chromosome-positive after two or more tyrosine kinase inhibitors (TKIs) were eligible. Single-agent CN201 was administered intravenously once per week with a step-up dose approach during cycle 1, a priming dose on Day 1 followed by an intermediate dose on Day 8 and the target dose administered on Day 15 and thereafter. The patients will receive 2 cycles of CN201 for induction. Responders will continue to receive a further 3 cycles for consolidation, and up to an additional 7 cycles for maintenance treatment or until PD or unacceptable toxicity. Results: As of January 31, 2024, 42 adult patients received CN201 with full dose from 600 μg to 40mg. 37 patients were evaluable for efficacy (Table1). Maximum tolerated dose has not reached. The most common adverse events (≥20%) of grade 3 or higher were leukopenia (47.6%), lymphopenia (42.9%), neutropenia (38%), thrombopenia (33.3%) , anaemia (26.2%). 6 patients (14.3%) had infections of grade 3 or higher. Cytokine release syndrome occurred in 13 (30.9%) patients, mainly occurred following the first dose, most were low-grade, except for one patient with grade 3. No immune effector cell-associated neurotoxicity syndrome was observed. Overall, 11 (30%) of 37 patients had complete remission (CR), 1 (2.7%) patient had complete remission with incomplete haematological recovery (CRi), 75% of responders had MRD negativity. The CR rate significantly increased with dose descalation, reached 50% (4 of 8 patients) with 10mg target dose, two of those occurred within the first two weeks following CN201 treatment. Among those responders, 100% were MRD negative. The CR rate in patients with higher dose levels are under investigation. Conclusions: Preliminary data show CN201 has a well tolerable safety profile and promising activity in adult patients with relapsed or refractory ALL. Clinical trial information: NCT05579132 . [Table: see text]