Selpercatinib (LOXO-292) in patients with RET-Fusion+ non small-cell lung cancer(NSCLC)

Background: Selpercatinib (LOXO-292) is a highly selective and potent small-molecule RET kinase inhibitor. We report anupdate on selpercatinib's efficacy and safety in RET-fusion+ NSCLC. Methods: Patients with RET-fusion+ NSCLC were enrolled to global, multicentre, Phase 1/2 LIBRETTO-001 trial. FollowingPhase 1 dose escalation, patients received the recommended dose (160 mg orally BID. Primary endpoint: objectiveresponse rate (ORR). Secondary endpoints included duration of response (DoR) and safety. Primary analysis set was defined as the first 105 enrolled patients previously treated with platinum-based chemotherapy. Treatment-naïve patientswere analyzed separately. Cutoff date for all analyses:16Dec2019 data. Results: In primary analysis set (platinum-treated patients, median 3 prior systemic regimens; range 1-15), investigator-assessed ORR: 70%(95%CI:59.8-78.1, n = 73/105). Responses did not differ by fusion partner or number/type of priortherapies, including anti-PD-1/PD-L1 agents and off-label multikinase inhibitors. Median DoR:20.3 months (95%CI:15.6-24.0) (45/73 [62%] responders censored at median follow-up of 14.8 months). Among 39 treatment-naïve patients,investigator-assessed ORR: 90%(95%CI:75.8-97.1, n = 35/39 [2 responses pending confirmation]). Median DoR was notreached (27/33 [82%] confirmed responses ongoing at median follow-up of 7.4 months). Safety analysis set comprised allselpercatinib dosed patients (N = 702), most common treatment-related adverse events (TRAEs) occurring in ≥ 15%patients: dry mouth(33.3%),increased AST(24.5%), increased ALT(23.8%), hypertension(23.2%), diarrhea(19.7%),fatigue(16.8%). Only 2%(n = 14/702) patients discontinued selpercatinib for TRAEs. Conclusions: Selpercatinib achieved marked and durable antitumor activity in patients with RET-fusion+ NSCLC.Selpercatinib was well tolerated. Efficacy data assessed by independent review committee based on the cutoff date will bepresented.