Patients
Adult patients (≥18 years of age) with MET -dysregulated advanced solid tumors refractory to currently available therapies or for which no effective therapy was available were enrolled in this study.MET -dysregulation was defined as either MET amplification (determined by fluorescence in situ hybridization or quantitative polymerase chain reaction with a gene copy number ≥4) or METoverexpression (determined by MET immunohistochemistry intensity score +3 in ≥50% of tumor cells) or MET mutation (leading to exon 14 deletion). Other inclusion criteria included availability of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, and an adequate organ function. Prior to receiving capmatinib, patients must have recovered from any previous anticancer treatment-related toxicities to Grade ≤1 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. However, patients with any grade of alopecia were eligible.
Patients were excluded if they had known hypersensitivity to digoxin or rosuvastatin or any of the excipients of capmatinib, digoxin or rosuvastatin or have inadequate organ function. Patient receiving following treatments were excluded: digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase; strong or moderate in vivo inhibitors and inducers of CYP3A4 that cannot be discontinued at least 1 week prior to the start of treatment with capmatinib and for the duration of the study; in vivo inhibitors or inducers of P-gp or BCRP within 30 days prior to starting study treatment, or during the DDI phase; medicines with a known risk of prolonging the QT interval; unstable or increasing doses of corticosteroids; proton pump inhibitors within 7 days prior to starting study treatment or during the DDI phase; thoracic radiotherapy to lung fields ≤4 weeks prior to starting the capmatinib or patients who did not recover from radiotherapy-related toxicities; major surgery (except video-assisted thoracic surgery and mediastinoscopy) within 4 weeks prior (2 weeks for resection of brain metastases) to starting capmatinib or patients who did not recover from side-effects of such procedure; homeopathic or naturopathic medicines (except vitamin supplements) within 5 days prior to the days of blood sample collection for pharmacokinetic assessment in the DDI phase (i.e., Day 5 to Day 10 and Day 17 to Day 32 of the DDI phase).
This clinical study was designed and implemented in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Council for Harmonization, with applicable local regulations. The study protocol and all amendments were reviewed by the independent ethics committee or institutional review board for each center. All patients provided written informed consent before screening.