MK-4830

Overview

MK-4830 is a first‑in‑class human IgG4 monoclonal antibody developed by Merck that targets the myeloid inhibitory receptor ILT4 (also known as LILRB2/CD85d). It is being studied alone and in combination with pembrolizumab across advanced solid tumors. A first‑in‑human Phase 1 study (NCT03564691) reported acceptable safety, pharmacodynamic target engagement, and early antitumor activity, notably when combined with pembrolizumab in heavily pretreated patients, including some who had progressed on prior PD‑1/PD‑L1 therapy. (aacrjournals.org)

Ongoing/related development includes expansion cohorts in multiple tumor types within NCT03564691 and a coformulation arm (MK‑4830A: MK‑4830 800 mg + pembrolizumab 200 mg). A separate randomized Phase 2 neoadjuvant ovarian cancer study (MK‑4830‑002; NCT05446870) was completed with results posted, using ctDNA reduction at Cycle 3 as the primary endpoint. (clinicaltrials.ucsf.edu)

Mechanism of action

ILT4/LILRB2 is an inhibitory receptor expressed primarily on myeloid cells that binds HLA‑G and other MHC class I ligands to transduce immunosuppressive signals via SHP phosphatases, fostering a suppressive tumor microenvironment. MK‑4830 binds ILT4 and blocks ligand engagement, aiming to reprogram myeloid cells and relieve suppression of antitumor T‑cell immunity. (aacrjournals.org)

Efficacy

• Dose‑escalation/early phase (advanced solid tumors; NCT03564691)
• Clinical Cancer Research report: Among 34 patients treated with MK‑4830 + pembrolizumab, 11 achieved objective responses; five responders had previously progressed on anti‑PD‑1/PD‑L1 therapy. (aacrjournals.org)

• ESMO 2020 initial results: ORR 24% (8/34) for MK‑4830 + pembrolizumab in heavily pretreated patients; durable responses reported. (merck.com)

• Expansion cohorts presented at AACR 2024 (previously treated populations)

• Head & neck (post‑platinum and post‑PD‑(L)1): ORR 0% (95% CI 0–10).
• Pancreatic adenocarcinoma (1–3 prior lines): ORR 6% (95% CI 1–20); median DOR 14.3 months.
• Glioblastoma (1 prior line): ORR 5% (95% CI 0–25).

• Gastric/GEJ adenocarcinoma (≥2 prior regimens): ORR 20% (95% CI 8–37); median DOR 9.6 months (3.0–27.6+). Investigators concluded activity was not beyond that historically seen with pembrolizumab monotherapy in these difficult‑to‑treat settings. (aacrjournals.org)

• Platform/other trials

• An esophageal cancer umbrella study discontinued the MK‑4830 combination arms per a 2023 protocol amendment. (merckclinicaltrials.com)
• The randomized Phase 2 neoadjuvant ovarian cancer study (MK‑4830‑002; NCT05446870) has completed with results posted (primary endpoint: early ctDNA reduction); peer‑reviewed efficacy outcomes beyond the abstract are not yet publicly detailed. (aacrjournals.org)

Overall, early signals suggest potential benefit of combining MK‑4830 with PD‑1 blockade in select settings, with mixed activity across tumor‑specific expansion cohorts that were predominantly heavily pretreated. (aacrjournals.org)

Safety

• First‑in‑human study: No dose‑limiting toxicities observed; maximum tolerated dose not reached. Safety was acceptable for MK‑4830 alone and with pembrolizumab. In early data presented at ESMO 2020, treatment‑related AEs occurred in 48% with monotherapy and 54% with combination therapy, mostly grade 1–2. (aacrjournals.org)
• AACR 2024 expansion cohorts: No treatment‑related deaths were reported; the combination was described as having a manageable adverse‑event profile. (aacrjournals.org)

Reported toxicities have been consistent with those expected for PD‑1–based regimens, without new safety signals clearly attributable to MK‑4830. (aacrjournals.org)

Key trials (selected)

• NCT03564691: Phase 1 multi‑arm study of MK‑4830 ± pembrolizumab with multiple expansion cohorts; includes a coformulation arm (MK‑4830A). Status: active, not recruiting (estimated completion September 2025). (clinicaltrials.ucsf.edu)
• NCT05446870 (MK‑4830‑002): Randomized Phase 2 neoadjuvant study in high‑grade serous ovarian cancer (pembrolizumab + chemotherapy ± MK‑4830); completed with results posted (primary endpoint: ΔctDNA at Cycle 3). (cdek.pharmacy.purdue.edu)

Further reading

• Clinical Cancer Research (first‑in‑human study with translational analyses). (aacrjournals.org)
• AACR 2024 late‑breaking abstract: tumor‑specific expansion cohorts (pancreatic, glioblastoma, HNSCC, gastric/GEJ). (aacrjournals.org)
• ESMO 2020 initial results and OncologyPRO summary. (merck.com)
• Review of myeloid checkpoints (context for ILT4/LILRB2 biology). (pmc.ncbi.nlm.nih.gov)
• Trial listings and status updates (NCT03564691; NCT05446870). (clinicaltrials.ucsf.edu)

Last updated: Oct 2025