MK-4830

Shows activity

Cancer types include:

cervical cancer esophageal cancer head and neck cancer non-small cell lung cancer small cell lung cancer

TrialFetch AI Analysis

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Overview

MK-4830 is an investigational cancer immunotherapy studied alone and, more often, with pembrolizumab and sometimes chemotherapy. Human results are available from early-phase trials, but the reported combination studies do not establish how much benefit MK-4830 adds to the other drugs. (aacrjournals.org)

Mechanism of action

MK-4830 is a human IgG4 monoclonal antibody that targets immunoglobulin-like transcript 4 (ILT4), an inhibitory receptor on myeloid immune cells. Blocking ILT4 is intended to reduce immune suppression in tumors and support antitumor T-cell activity, potentially alongside PD-1 blockade. (aacrjournals.org)

Efficacy

In a first-in-human phase 1 dose-escalation study of advanced solid tumors, 11 of 34 patients (32%) receiving MK-4830 plus pembrolizumab had an objective response; five responders had previously experienced disease progression on anti–PD-1/PD-L1 treatment. Fifty patients received MK-4830 alone in the same study. (aacrjournals.org)

Later results were mixed. In a phase 1/2 study of previously untreated, PD-L1-positive advanced non-small-cell lung cancer, 15 of 60 patients (25%) responded to MK-4830 plus pembrolizumab. The investigators described its activity as similar to that previously observed with pembrolizumab alone. A separate phase 1 expansion reported response rates of 28% in ovarian cancer, 32% in triple-negative breast cancer, and 38% in mesothelioma with MK-4830, pembrolizumab, and chemotherapy; these results cannot isolate MK-4830’s contribution. (annalsofoncology.org)

Safety

The first-in-human dose-escalation study found no dose-limiting toxicities or treatment-related deaths. Grade 3–4 treatment-related adverse events occurred in 3 of 50 patients (6%) receiving MK-4830 alone and 4 of 52 (8%) receiving the combination, including patients who crossed over from monotherapy. In the later lung-cancer combination study, 11 of 60 (18%) had grade 3 or higher treatment-related adverse events. The three chemotherapy-combination cohorts reported grade 3–5 treatment-related adverse events in 34%–45% of patients and three treatment-related deaths across the cohorts; those events were attributed to the treatment regimens, not specifically to MK-4830. (aacrjournals.org)

Active trials using MK-4830

Found 3 active trials using this drug:

A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B

Sponsor: Merck Sharp & Dohme LLC (industry) Phase: 1/2 Start date: May 16, 2023

TrialFetch AI summary: Adults with unresectable locally advanced or metastatic esophageal squamous cell carcinoma progressing after one platinum- and PD-1/PD-L1–containing regimen receive investigator-selected paclitaxel or irinotecan, or investigational sacituzumab tirumotecan, a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor. Arms combining pembrolizumab with the anti-ILT4 antibody MK-4830 and either chemotherapy or lenvatinib are no longer enrolling.

ClinicalTrials.gov ID: NCT05319730

A Phase 1b/2 Study to Evaluate the Efficacy and Safety of Investigational Agents as Monotherapy or in Combination With Pembrolizumab for the Treatment of Participants With PD-1/L1-refractory Extensive-Stage Small Cell Lung Cancer in Need of Second-Line Therapy (KEYNOTE-B98)

Sponsor: Merck Sharp & Dohme LLC (industry) Phase: 1/2 Start date: Aug. 19, 2021

TrialFetch AI summary: Adults with extensive-stage SCLC progressing after exactly one platinum-based regimen containing a PD-1/PD-L1 inhibitor receive second-line investigational treatment; eligibility requires ECOG 0–1 and measurable disease. Regimens include pembrolizumab plus the CTLA-4 inhibitor quavonlimab, alone or with the multikinase inhibitor lenvatinib or ILT4 inhibitor MK-4830; pembrolizumab plus the LAG-3 inhibitor favezelimab; or R-DXd, a CDH6-targeted antibody–drug conjugate carrying a topoisomerase I inhibitor.

ClinicalTrials.gov ID: NCT04938817

KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

Sponsor: Merck Sharp & Dohme LLC (industry) Phase: 1/2 Start date: Dec. 19, 2019

TrialFetch AI summary: Adults with previously untreated stage IV squamous or nonsquamous NSCLC receive pembrolizumab-based therapy, with chemotherapy according to histology. Investigational combinations add the TIGIT inhibitor vibostolimab, CD27 agonist boserolimab, ILT4 inhibitor MK-4830, or ILT3 inhibitor MK-0482 to pembrolizumab and chemotherapy, or pair pembrolizumab with the B7-H3–directed antibody–drug conjugate ifinatamab deruxtecan or the HER3-directed antibody–drug conjugate HER3-DXd, with or without carboplatin.

ClinicalTrials.gov ID: NCT04165070