The MK-1084-004 Study

The KRASG12C mutation occurs in approximately 12% of patients with non-small cell lung cancer making it one of the more common oncogenic drivers in this setting. Previously, results of a phase I trial demonstrated a manageable safety profile and promising antitumor activity with a combination of the selective KRASG12C inhibitor MK-1084 and pembrolizumab in patients with previously untreated NSCLC with PD-L1 TPS ≥1%. These findings formed the basis for the randomized, phase III MK-1084-004 Study. The design of this trial was presented as a poster by Dr Maximilian Hochmair (Klinik Floridsdorf, Vienna, Austria) during the 2024 annual ESMO meeting.

To be eligible for this trial, patients must be ≥18 years with histologically or cytologically confirmed stage IV NSCLC (by AJCC v8), harbour a KRASG12C mutation and have a PD-L1 tumour proportion score of ≥50%. Patients in the study are randomized (1:1) to receive pembrolizumab (200 mg IV q3w) in combination with MK-1084 (100 mg qd) or placebo. This randomization is stratified by ECOG PS, the presence of brain metastases, and prior immunotherapy in the neoadjuvant/adjuvant setting. The primary endpoints of the study are progression-free (PFS) and overall survival (OS).