RW Effectiveness of Capmatinib in Advanced MET-dysregulated NSCLC Included in the French Compassionate Use Program (ATU)

Capmatinib has been approved in the USA and Japan. In France, a compassionate use for capmatinib has been approved in June 2019 for patients with MET alterations, including METex14 mutations and MET amplification. In March 2021, 204 patients are or have been treated with compassionate use capmatinib as part of this program, most of them (n=175) harboring a METex14 mutation. So far, data on activity and safety of new-generation MET TKIs are still sparse and only based on prospective clinical studies. The CapmATU study is a unique opportunity to describe patients' characteristics and outcomes, and confirm effectiveness of capmatinib in a large cohort of METex14 NSCLC. Moreover, it will provide original real-world evidence (RWE). RWE can be used in oncology to further characterize the safety and efficacy of drugs in the post-marketing setting. This may include confirmation of clinical benefit for regulatory purposes, expansion of labeling claims to new indications, testing of alternate doses and schedules of drugs, and assessment of drug activity in biomarker-defined subgroups and other special populations. This may be even more important in the context of METex14 NSCLC patients since no real world data with new generation MET TKIs have been reported so far. Indeed, this study will allow to determine whether the antitumor activity of capmatinib reported in the GEOMETRY-MONO-1 study can be observed in less selected patients. Given the older age and associated comorbidities of METex14 NSCLC patients, most of them may not be eligible to a clinical trial, thus emphasizing the need for real-world evidence. Finally, the biological part of this study (CapmATU-BIO) will offer opportunity to identify biomarkers of sensitivity or acquired resistance to capmatinib, which is a poorly explored field of research so far. In this context, the objectives of this non-interventional retrospective French population-base study are to describe the characteristics of patients with MET-dysregulated NSCLC, assess effectiveness and safety of capmatinib in these patients and identify biomarkers of benefit from capmatinib.