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First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance
Lillian L Siu1, Ding Wang2, John Hilton3
1Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada. Lillian.siu@uhn.ca.
MK-4830, a novel immunotherapy targeting ILT4, showed good tolerability and antitumor activity in advanced solid tumors. Combination therapy with pembrolizumab demonstrated promising responses, especially in patients with moderate T-cell inflammation.
Area of Science:
- Immunotherapy
- Oncology
- Clinical Trials
Background:
- Novel immunotherapies are crucial for treating advanced solid tumors.
- Targeting the immunoglobulin-like transcript 4 (ILT4) receptor presents a potential therapeutic strategy.
- Understanding the tumor microenvironment's role in immune evasion is key.
Purpose of the Study:
- To evaluate the safety and efficacy of MK-4830, a first-in-class anti-ILT4 antibody.
- To assess MK-4830 as monotherapy and in combination with pembrolizumab in advanced solid tumors.
- To explore biomarkers associated with treatment response.
Main Methods:
- First-in-human study (NCT03564691) with dose escalation of MK-4830.
- Patients with advanced solid tumors received MK-4830 monotherapy or combination therapy with pembrolizumab.
- Safety, pharmacokinetics, objective response rate (RECIST v1.1), and molecular biomarkers were assessed.
Main Results:
- MK-4830 was well tolerated; maximum tolerated dose was not reached.
- Dose-related target engagement and antitumor activity were observed.
- Objective responses were seen in 11/34 patients on combination therapy, including 5 with prior progression on anti-PD-1/PD-L1 therapy.
Conclusions:
- MK-4830, as monotherapy or combined with pembrolizumab, is well tolerated and shows antitumor activity.
- ILT4 targeting may enhance anti-PD-1/PD-L1 efficacy by modulating the myeloid-suppressive tumor microenvironment.
- ILT4 is a promising target for novel immunotherapy combinations.
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