Patient disposition
A total of 32 patients were enrolled in the study. Of these, 26 patients (81.3%) completed the DDI phase. The reasons for DDI phase discontinuation were AEs (two patients [6.3%]), physician’s decision (two patients [6.3%]), disease progression (one patient [3.1%]) and death (one patient [3.1%], Table 1 ). Of the two patients who discontinued the DDI phase due to AEs, one had experienced Grade 3 blood bilirubin and Grade 4 encephalopathy (both non-treatment related), and another patient had experienced Grade 3 abdominal pain and Grade 3 vomiting, both were treatment-related.
A total of 27 patients (84.4%) entered the treatment (post-DDI) phase, all of whom discontinued the study; the primary reason for discontinuation was PD (20 patients [62.5%]). Three patients (9.4%) discontinued from the treatment phase (post-DDI) due to physician decision and one patient each (3.1%, each) discontinued due to AE (Grade 3 pulmonary embolism; non-treatment related) and being lost to follow-up. Two patients (6.3%) died during the post-DDI phase; one due to PD and another due to Grade 3 respiratory tract infection (non-treatment related). One patient (3.1%) entered the post-treatment follow-up phase. However, this patient was discontinued due to protocol deviation. The patient received rosuvastatin during the DDI phase except on Day 1 and Day 22. All 32 patients enrolled in the study were included in the full analysis set and safety set. Of these, 25 (78.1%), 24 (75.0%), and 17 (53.1%) patients were included in pharmacokinetic analysis set for digoxin, rosuvastatin, and capmatinib, respectively.