WCLC 2022 | Phase I A study evaluating GDC-6036 monotherapy in patients with NSCLC with KRAS G12C mutation

At World Lung this year, I presented the results of a Phase I study of GDC-6036, looking at metastatic or advanced solid tumors broadly, but focusing on the subset of patients that had non-small cell lung cancer with a KRAS G12C mutation. the goal of the study was to understand the safety and tolerability, the pharmacokinetics, and the anti-tumor activity of GDC-6036. So the study included both a dose-escalation cohort, where patients were treated at increasing doses of GDC-6036, and then in expansion cohort where patients were treated at the planned highest dose of 400 milligrams once daily. The trial that I presented demonstrated that GDC-6036 was a very tolerable drug.

The most common adverse events that patients experienced were nausea, vomiting, and diarrhea, but the vast majority of those episodes were low grade and were managed with symptomatic intervention. There was a small number of patients that experienced liver abnormalities, mainly the non-small cell lung cancer patients, but the frequency was quite low. In total, approximately 18% of patients had to have dose reductions on study, but only 5% of patients had to discontinue drug due to toxicity. Generally GDC-6036 appeared to be very tolerable. In terms of the activity of GDC-6036, we were able to demonstrate, even at this early time point, an unconfirmed response rate of 53% and a confirmed response rate of 46%, implying that GDC-6036 is a very active drug. In addition to that, looking at the pharmacokinetics and the pharmacodynamics of the drug, they are compatible with once daily dosing, which is more convenient, and also demonstrate a high degree of target engagement when we look at, on treatment biopsies from patients that were in the study.