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).
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.
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.
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.
NCT03564691.
Medical writing and/or editorial assistance was provided by Holly C. Cappelli and Dana Francis of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
L.L. Siu: Honoraria (institution): Arvinas; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Officer/Board of Directors: AACR; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/Medimmune; Advisory/Consultancy: MorphoSys; Advisory/Consultancy: Roche; Research grant/Funding (institution): Roche/Genetech; Advisory/Consultancy: Loxo; Advisory/Consultancy: Oncorus; Advisory/Consultancy, Research grant/Funding (institution): Symphogen; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Voronoi; Advisory/Consultancy: Treadwell Therapeutics; Advisory/Consultancy: Tessa; Advisory/Consultancy: Navire; Advisory/Consultancy: Relay Therapeutics; Advisory/Consultancy: Rubius Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Intensity Therapeutics; Research grant/Funding (institution): Mirati, Shattucks, and Avid. R. Geva: Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses: Medison; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Janssen; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: BOL Pharma; Travel/Accommodation/Expenses: Merck. D. Rasco: Research grant/Funding (institution): Merck. A.K. Abraham: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. J.F. Markensohn: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. L. Suttner: Full/Part-time employment: Merck; Research grant/Funding (self): GlaxoSmithKline. S. Siddiqi: Full/Part-time employment: Merck. R.A. Altura: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. C. Maurice-Dror: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Medison; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.