Dr. Gutierrez on Biomarker-Directed Precision Oncology 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.