Martin E. Gutierrez, MD, Cancer Genetics, Gastrointestinal Medical Oncology, Thoracic Medical Oncology, Hackensack Meridian Health, discusses the investigation of MK-0482 in advanced solid tumors. 

A phase 1 trial (NCT03918278) is evaluating MK-0482, a novel humanized IgG4 mon0clonal antibody targeting immunoglobulin-like transcript 3 (ILT3), both as a single agent and in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors.

ILT3 is an inhibitory receptor that is highly expressed on monocytic myeloid cells, including dendritic cells, macrophages, monocytes, and myeloid-derived suppressor cells, Gutierrez explains. Since myeloid-derived suppressor cells inhibit T-cell function, they are considered the primary driver of immunosuppression in the tumor microenvironment, Gutierrez explains.

By targeting ILT3, MK-0482 is designed to relieve immunosuppression and improve clinical benefit when combined with a PD-1 inhibitor such as pembrolizumab, Gutierrez concludes.

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Martin E. Gutierrez, MD, discusses the investigation of MK-0482 in advanced solid tumors. 

Dr. Gutierrez on the Investigation of MK-0482 in Advanced Solid Tumors

Martin E. Gutierrez, MD, director, co-chief and medical oncologist, Divisions of Thoracic Oncology and Gastrointestinal Oncology, John Theurer Cancer Center, Hackensack University Medical Center, discusses the safety profile of pembrolizumab (Keytruda)-based combination strategies in non-small cell lung cancer (NSCLC).

In the phase II KEYNOTE-495/KeylmPaCT trial (NCT03516981), patients with treatment-naïve, advanced NSCLC who do not harbor 

 gene rearrangements will be grouped into 4 categories depending on their T cell-inflamed gene expression profile and tumor mutational burden. Each group will be randomized to receive pembrolizumab plus either MK-4280, lenvatinib (Lenvima), or the CTLA-4 inhibitor MK-1308.

The recommended phase II dose of MK-1308 and pembrolizumab has been established, says Gutierrez. A slight increase in immune-related adverse events was reported with the combination; however, this was expected. According to phase I data, MK-4280 was well tolerated. Regarding the combination of pembrolizumab and lenvatinib, investigators have yet to see an increase in toxicity beyond what is expected with lenvatinib alone, concludes Gutierrez.

Dr. Gutierrez on the Safety Profile of Pembrolizumab-Based Combos in NSCLC

Martin E. Gutierrez, MD, director, co-chief and medical oncologist, Divisions of Thoracic Oncology and Gastrointestinal Oncology, John Theurer Cancer Center, Hackensack University Medical Center, discusses the biomarker-directed precision oncology of pembrolizumab-based (Keytruda) combination therapy in the treatment of patients with non—small cell lung cancer (NSCLC).

The phase II KEYNOTE-495/KeyImPaCT study (NCT03516981) will enroll patients with treatment-naïve, advanced NSCLC, with a documented absence of EGFR and BRAF mutations, ROS1 gene rearrangements, and measurable disease. Patients will have tissues screened for 2 biomarkers: T cell-inflamed gene expression profile (GEP) and tumor mutational burden (TMB). Patients will then be assigned to one of four groups: those who are TMB-low and GEP-low, TMB-high and GEP-low, TMB-low or GEP-high, and TMB-high and GEP-high, explains Gutierrez.

Patients in each of these groups will then be randomized to receive a pembrolizumab-based combination. Combinations include pembrolizumab plus MK-4280, pembrolizumab plus lenvatinib (Lenvima), and pembrolizumab plus MK-1308, a CTLA-4 inhibitor. Treatment will continue for 35 cycles, approximately 2 years. Patients will be assessed for response to treatment via imaging every 9 weeks for the first year and 12 weeks thereafter.

The primary objective of the study is to evaluate the objective response rate of patients to figure out which pembrolizumab combination provides the best efficacy for each patient population based on their molecular profile, according to Gutierrez. The secondary objectives are progression-free survival, overall survival, and safety.

Martin E. Gutierrez, MD, discusses the biomarker-directed precision oncology of pembrolizumab-based combination therapy in the treatment of patients with non–small cell lung cancer.

Martin E. Gutierrez, MD

Articles

Dr. Gutierrez on the Investigation of MK-0482 in Advanced Solid Tumors

Dr. Gutierrez on the Safety Profile of Pembrolizumab-Based Combos in NSCLC

Dr. Gutierrez on Biomarker-Directed Precision Oncology of Pembrolizumab-Based Combos in NSCLC