MK-0482 is a novel humanized IgG4 monoclonal antibody that targets ILT3, potentially alleviating immunosuppression within the tumor microenvironment. In the expansion cohort of the first-in-human Phase I study (MK-0482-001), the combination of MK-0482, pembrolizumab, and gemcitabine/nab-paclitaxel was evaluated in patients with treatment-naive metastatic pancreatic ductal adenocarcinoma.

The primary endpoint of the study was safety, while secondary endpoints included objective response rate, disease control rate (complete response, partial response, and stable disease), and duration of response as assessed by investigators.

A total of 37 patients were enrolled and received the study treatment. As of the data cutoff on October 3, 2023, the median follow-up was 13 months. The median age of the patients was 65 years. All patients experienced adverse events, with 97% experiencing treatment-related adverse events. Grade 3 or 4 treatment-related adverse events occurred in 73% of patients, with the most common being decreased neutrophil count (27%), anemia (19%), and neutropenia (19%). No treatment-related deaths occurred. Immune-mediated adverse events occurred in 32% of patients, the most frequent being hypothyroidism (11%). Grade 3 immune-mediated adverse events occurred in 14% of patients, including hepatitis, severe skin reactions, and colitis. There were no Grade 4 or 5 immune-mediated events.

The confirmed objective response rate was 43%, and the disease control rate was 84%. The median duration of response was 8.5 months. The median progression-free survival was 8.5 months, and the median overall survival was 15.6 months. The 12-month progression-free survival and overall survival rates were 35% and 60%, respectively. Biomarker data were presented at the ASCO conference.

KOL insights

“ILT3 is an inhibitory receptor that is highly expressed on monocytic myeloid cells, including dendritic cells, macrophages, monocytes, and myeloid-derived suppressor cells. Since myeloid-derived suppressor cells inhibit T-cell function, they are considered the primary driver of immunosuppression in the tumor microenvironment, by targeting ILT3, MK-0482 is designed to relieve immunosuppression and improve clinical benefit when combined with a PD-1 inhibitor such as pembrolizumab.” –Expert Opinion.

Conclusion

As per Delveinsight’s estimates, there were approximately 60,000 incident cases of Pancreatic Cancer in the United States in 2023. The combination of MK-0482, pembrolizumab, and Gem/Nab-P demonstrated a manageable adverse event profile in treatment-naive metastatic pancreatic ductal adenocarcinoma (mPDAC) patients, aligning with the known safety profiles of pembrolizumab-based immunotherapy and Gem/Nab-P. This four-drug regimen exhibited enhanced clinical efficacy compared to traditional chemotherapy treatments. Further evaluation is necessary to confirm these promising clinical outcomes.