Efficacy and Safety Analysis of Selpercatinib in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer-Results from the Japanese Subset of a Global Phase 1/2 Study

PURPOSE: Selpercatinib is a highly selective, potent, rearranged during transfection(RET)inhibitor. A global, multicenter, open-label, phase 1/2 study of selpercatinib(LIBRETTO-001, NCT03157128)has been ongoing since 2017. We evaluated the data of Japanese patients with RET fusion-positive non-small cell lung cancer(NSCLC)using 30 March 2020 cut-off data. METHODS: Phase 2 of LIBRETTO-001 started after confirming the safety of the recommended phase 2 dose(160 mg bid, orally, 28-day cycles)in Japanese. The primary endpoint was the independently assessed objective response rate(RECIST v1.1). RESULTS: Japanese NSCLC patients, including 44 patients in cohort 1 who had previously received platinum-based(or other)chemotherapy, programmed cell death-1/programmed death-ligand 1 immunotherapy, or both, and four previously untreated patients in cohort 2, were analyzed. The objective response rate was 55.3%(95% confidence interval: 38.3, 71.4; one confirmed complete response, 20 confirmed partial responses)in 38 evaluable patients in cohort 1 who could be followed for ≥2 post-baseline scans. The only evaluable patient in cohort 2 had no response. The most frequent treatment- emergent adverse events were increased alanine aminotransferase, increased aspartate aminotransferase, and diarrhea. CONCLUSIONS: Selpercatinib appeared to be effective in Japanese patients with RET fusion-positive NSCLC, and the safety profile was not substantially different from published results.