Sotorasib in Advanced KRASG12C-mutated Non-small Cell Lung Cancer Patients With Comorbidities

A single-arm multi-institutional phase II study to investigate sotorasib in KRASG12C-mutated non-small cell lung cancer stage III/IV not amenable for curative treatment including patients with comorbidities, and to provide translational knowledge regarding mechanism of relapse and differences in responses, including differences among patients with different co-occurring mutations. The aim is to investigate whether treatment with sotorasib will provide significant objective response rates in predefined KRASG12C-mutated non-small cell lung cancer patients that are not typically included in phase III-studies. Furthermore, the trial will explore whether patients in performance status ECOG 2 may benefit from sotorasib. In this study, a relevant number of sotorasib-naïve patients (n=100) will be treated with sotorasib and followed for efficacy and side effects. MRI-scans both at base-line and regularly during therapy will give data on intracranial efficacy. Eligible patients will be previously treated with at least 1 line standard (chemo)immunotherapy, or deemed in-eligible for standard (chemo)immunotherapy. In part II of the study, comprehensive analyses of biological samples taken pretreatment, and post-progression will provide novel information about resistance mechanisms on sotorasib. Furthermore, analyses of biopsies taken at partial response (estimated to be performed in 25-30% of cases) may potentially also characterize non-eradicated residual cells after achieved response. The post-progression biopsies may indicate the optimal next-line therapy.