Merck (MSD) has launched a Phase III clinical trial of its investigational oral selective Kirsten rat sarcoma glycine 12 to cysteine (KRAS G12C) inhibitor, MK-1084, plus KEYTRUDA to treat certain metastatic non-small cell lung cancer (NSCLC) patients.
This study will analyse the combination regimen as first-line treatment for metastatic NSCLC patients with tumours exhibiting KRAS G12C mutations and programmed death-1 ligand 1 (PD-L1) expression.
The double-blind, randomised, multicentre trial will assess the safety and effectiveness of MK-1084 plus KEYTRUDA against KEYTRUDA with a placebo.
Approximately 600 previously untreated patients with metastatic NSCLC with KRAS G12C mutations and a PD-L1 tumour proportion score (TPS) TPS of 50% or more from across the globe will be enrolled in the trial.
Progression-free survival and overall survival are the study's primary endpoints.
Key secondary endpoints of the trial are objective response rate and duration of response.
Merck is developing MK-1084 in partnership with Taiho Pharmaceutical and Otsuka Pharmaceutical subsidiary Astex Pharmaceuticals under a deal signed in 2020.
The asset is currently being analysed in an open-label, multicentre Phase I trial to assess the safety, tolerability, pharmacokinetics, and efficacy as both a monotherapy and as a combination regimen in KRAS G12C mutant advanced solid tumour patients.
Merck Research Laboratories oncology global clinical development head and senior vice-president Dr Marjorie Green said: “KRAS is among the most prevalent mutations in cancer and KRAS G12C is the most common KRAS mutation in patients with non-small cell lung cancer.
“Based on early evidence showing MK-1084 in combination with KEYTRUDA had a manageable safety profile and promising anti-tumour activity, we are now proceeding to a larger Phase III trial to evaluate this combination in certain patients with metastatic non-small cell lung cancer.”
Last month, the company reported that the Phase III KEYNOTE-A18 trial of Keytruda plus chemoradiotherapy (CRT) in cervical cancer patients met the primary endpoint.
