https://orcid.org/0000-0001-9573-2690
Key Points
IO-202, a first-in-class anti-LILRB4 antibody, is well-tolerated as monotherapy or in combination with azacitidine (AZA) in CMML and AML.
IO-202 in combination with AZA generated rapid responses with multiple significant clinical benefits in hypomethylating agent-naïve CMML.
Abstract
IO-202 is a humanized IgG1 monoclonal antibody with high affinity and specificity for leukocyte immunoglobulin-like receptor B4 (LILRB4, ILT3), which is predominantly expressed in monocytes and monocytic blasts. IO-202 induces antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in vitro and in leukemia patients. Herein, we present the Phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R chronic myelomonocytic leukemia (CMML), and the Phase 1b dose expansion data of IO-202 combined with AZA for the treatment of hypomethylating agent (HMA)-naïve CMML (NCT04372433). IO-202 was well-tolerated as monotherapy and in combination with AZA. Patients with R/R monocytic AML expressing high LILRB4 on leukemia blasts demonstrated clinical activity, including a complete response (CR) in dose escalation with IO-202 + AZA. In HMA-naïve CMML patients, IO-202 + AZA led to a 27.8% CR rate and 66.7% overall response rate, based on the 2015 International Working Group response criteria for myelodysplastic/myeloproliferative neoplasms. All 18 efficacy-evaluable HMA-naïve CMML patients (100%) achieved some type of investigator-assessed clinical benefit, including symptomatic improvement, decrease in transfusions, decreased blasts and/or monocytes, and resolution of thrombocytopenia. Seven patients (38.9%) proceeded to allogeneic hematopoietic cell transplantation. Translational data suggest that efficacy favors patients with high LILRB4 expression, supporting the mechanism of action of IO-202. Overall, the data support a future pivotal study of IO-202 + AZA in HMA-naïve CMML patients.
Author notes
A.A. and G.N.M. contributed equally to this study.
Data Sharing: The study protocol is included in supplemental data available with the online version of this article. Individual participant data will not be shared beyond what have been comprehensively presented in this article.
