Background: Selpercatinib, is a first-in-class, highly selective, CNS active and potent RET inhibitor approved in multiple countries for treatment of RET-fusion positive lung or thyroid cancers. Reported is an update of efficacy and safety results in RET-altered thyroid cancer, with a longer follow up (30 Mar 2020 data cutoff vs 16 Dec 2019) and additional enrolment. Methods: Patients (pts) with RET-mutant medullary thyroid cancer (MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in the global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial (NCT03157128). The primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), and safety. The integrated analysis set (IAS, n = 143) includes efficacy evaluable MTC pts previously treated with cabozantinib and/or vandetanib (cabo/vande). The primary analysis set (PAS), a subset of IAS, is the first 55 enrolled pts. Cabo/vande naïve MTC pts (N = 112) and TC pts with prior systemic treatment (N = 22) were also analyzed. Safety population includes all pts who received ≥1 dose of selpercatinib (MTC N = 315; TC N = 42) by data cutoff. Results: For MTC patients, the ORR for IAS was 69.2%, in the PAS it was 69.1%, and 71.4% for cabo/vande naïve MTC pts. The ORR for TC pts (n = 22) was 77.3% (see table). Most treatment-emergent adverse events (TEAEs) were low grade; the most common (≥25% of MTC and/or TC pts treated with selpercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipation for both MTC and TC pts, increased ALT/AST, peripheral edema and headache in MTC pts and nausea in TC pts. 4.8% of MTC and TC pts discontinued selpercatinib due to TEAEs but only 1.9% with MTC and none with TC discontinued due to treatment-related adverse events. Conclusions: In this updated analysis, selpercatinib continued to show marked and durable antitumor activity in pts with RET-altered thyroid cancers. Selpercatinib was well tolerated and no new safety concerns were identified. A global, randomized, phase 3 trial (LIBRETTO-531) evaluating selpercatinib compared to cabo/vande in kinase inhibitor naïve MTC pts is ongoing. Clinical trial information: NCT03157128

Clinical benefit rate, CBR; Complete response, CR; Not estimated, NE; Objective response rate, ORR; Partial response, PR; Progressive disease, PD; Stable disease, SD.