IO-202 Plus Azacitidine Shows Promise in Treating CMML
核心洞察
IO-202 combined with azacitidine achieved a 50% complete remission rate and a 66.7% overall response rate in CMML (搜索) patients naive to hypomethylating agents.
Notably, patients with high LILRB4 (搜索) expression showed an 83.3% complete remission rate and a 100% overall response rate with the combination therapy.
The combination enabled nearly 40% of patients to successfully undergo hematopoietic stem cell transplant, a potentially curative option.
Immune-Onc Therapeutics (搜索) presented updated data from its Phase 1b study of IO-202, a first-in-class anti-LILRB4 (搜索) antibody, in combination with azacitidine (AZA) for treating chronic myelomonocytic leukemia (搜索) (CMML (搜索)) patients. The findings, presented at the 2024 American Society of Hematology (ASH) Annual Meeting, highlight promising efficacy and safety results in hypomethylating agent-naive CMML patients.
The study revealed that the combination of IO-202 and AZA achieved a complete remission (CR) rate of 50.0% and an overall response rate (ORR) of 66.7% among the 18 efficacy-evaluable patients, based on the International Working Group (IWG) 2023 response criteria for higher-risk myelodysplastic syndromes. Notably, patients with high LILRB4 (搜索) expression achieved a CR rate of 83.3% (5/6) and an ORR of 100% (6/6).
Clinical Impact and Unmet Needs
CMML (搜索) is a rare form of blood cancer characterized by persistent elevation of peripheral blood monocytes and dysplastic features in the bone marrow. The prognosis for CMML patients remains poor, with a median survival of less than three years. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative option, yet fewer than 15-20% of patients are eligible. The current FDA-approved therapies, hypomethylating agents like azacitidine, yield modest CR rates of 7-17%.
"These results represent a positive advance in the treatment of CMML (搜索), a disease with very limited options and poor outcomes," said Gabriel N. Mannis, M.D., IO-202 Phase 1 investigator and associate professor of medicine, division of hematology, Stanford Cancer Institute, Stanford University. "Achieving a 50% complete response rate overall—and an 83% complete response rate in patients with high LILRB4 (搜索) expression—demonstrates the potential of IO-202 as a highly impactful therapy."
Study Details and Tolerability
In the Phase 1b study, treatment with IO-202 in combination with AZA enabled 38.9% of the patients to successfully bridge to HCT. Additionally, four out of six transfusion-dependent patients became transfusion-independent. IO-202 was well-tolerated at the preliminary recommended Phase 2 dose (60 mg/kg followed by 30 mg/kg every two weeks) among 21 safety-evaluable patients. No dose-limiting toxicities were reported.
Mechanism of Action and Future Directions
IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 (搜索), leading to the depletion of LILRB4-positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. This targeted approach has broad potential in blood cancers and autoimmune and inflammatory diseases.
"We are encouraged by the promising clinical activity and tolerability of IO-202 in this trial," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "These data support a pivotal study to evaluate IO-202 in combination with azacitidine as a frontline treatment for hypomethylating agent-naive CMML (搜索)."