A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia
Ahmed Aribi, Gabriel N. Mannis, Yazan F. Madanat, Brian A. Jonas, Neil Dunavin, Gail J. Roboz, Deepa Jeyakumar, Guillermo Garcia-Manero, Hongtao Liu, Hetty E. Carraway, Jennifer N. Saultz, William Blum, Gary J. Schiller, Tao Huang, Paul Woodard, Barbara Klencke, X. Charlene Liao, Hong Xiang, Daniel A. Pollyea, Courtney D. DiNardo
Abstract
IO-202 is a humanized immunoglobulin G1 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 and antibody-dependent cellular phagocytosis in vitro and in patients with leukemia. 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. 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 patients with HMA-naïve CMML, 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 patients with HMA-naïve CMML (100%) achieved some form of investigator-assessed clinical benefit, including symptomatic improvement, a decrease in transfusions, reduced 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 patients with HMA-naïve CMML. This trial was registered at www.clinicaltrials.gov as #NCT04372433.