Initial results of a phase I study of MK-4830, a first-in-class anti–immunoglobulin-like transcript 4 (ILT4) myeloid-specific antibody in patients (pts) with advanced solid tumours
Siu LL, Wang D, Hilton J, Geva R, Rasco D, Abraham AK, Markensohn JF, Suttner L, Siddiqi S, Altura RA, and Maurice-Dror C. Initial results of a phase I study of MK-4830, a first-in-class anti–immunoglobulin-like transcript 4 (ILT4) myeloid-specific antibody in patients (pts) with advanced solid tumours. Annals of Oncology 2020; 31:S462.
Annals of Oncology
Background: MK-4830 is a novel, first-in-class human IgG4 monoclonal antibody targeting the myeloid-specific ILT4 receptor. MK-4830 catalyzes reprogramming of tumour-associated macrophages, relieving myelosuppression and enhancing T cell function. We present data from the first-in-human phase I dose escalation study (NCT03564691) of MK-4830 and MK-4830 + pembrolizumab (pembro). Methods: Pts with advanced solid tumours received MK-4830 IV Q3W at escalating doses alone and with pembro. Primary end points were safety and tolerability. PK was a secondary end point; exploratory objectives included ORR per RECIST v1.1, evaluation of receptor occupancy (RO), and immune correlates of response in blood and tumour. Results: Among 84 pts, 50 received MK-4830 monotherapy; 34 received MK-4830 + pembro. Median age was 62 years; 50% previously received ≥3 lines of therapy. No dose-limiting toxicities were observed; maximum-tolerated dose was not reached. Any-grade AEs were consistent with those common to pembro. Treatment-related AEs were reported in 52% of pts; most were grade 1/2. MK-4830 steady-state serum PK at Ctrough was achieved at the highest dose levels, at which almost all pts had ≥95% blood RO. Preliminary efficacy data show 11 objective responses, with 2 complete responses and 9 partial responses; 1 response was observed in a patient receiving MK-4830 monotherapy. All responses occurred in heavily pretreated pts, 5 of whom had not had a response to prior anti–PD-1 therapy. Responses were durable; some pts received >1 year of treatment. Pre- and on-treatment (n=15) biopsies enabled a preliminary assessment of correlation between RO and immune cell subsets before and during treatment. Conclusions: This first-in-class MK-4830 antibody targeting ILT4 given as monotherapy and in combination with pembro was well tolerated and showed dose-related evidence of target engagement. Durable responses were observed with both MK-4830 alone and with MK-4830 + pembro in heavily pretreated pts, 5 of whom progressed on prior anti–PD-1 therapies. These initial data support the further development of MK-4830 + pembro for pts with advanced solid tumors. Clinical trial identification: NCT03564691.