2229P Updated safety and efficacy of selpercatinib in patients (pts) with RET-activated thyroid cancer: Data from LIBRETTO-001

Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-mutant MTC and RET fusion-positive thyroid and lung cancers. Updated analysis of selpercatinib in pts with RET fusion-positive thyroid cancer (TC), in LIBRETTO-001 (NCT03157128) was conducted after additional follow up (f/u) of 19 months. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression free survival (PFS), and safety. Efficacy of selpercatinib after RAI (where RAI appropriate) was evaluated in systemic treatment-naïve pts (N=24) and pre-treated pts (N=41) (Table). Naïve and pre-treated pts achieved an ORR of 95.8% and 85.4%, respectively (Table). For pre-treated pts DoR was 26.7 months and PFS was 27.4 months. DoR and PFS data for treatment-naïve pts are still immature approaching and at 2 years, with response ongoing in most pts. At 2 yrs, 95.2% of naïve pts and 57.1% of pre-treated pts remained progression free. In the safety population (N=66), the most common ≥3 grade treatment-emergent adverse events (TEAEs) were: hypertension (15.2%), hyponatraemia (10.6%), diarrhea (7.6%), lymphopenia (7.6%) and increased alanine aminotransferase (6.1%). Two pts (3.0%) discontinued treatment due to TEAEs; 1 pt (1.5%) of these was considered related.Table: 2229PTreatment naïve (N=24)Prior treatment (N=41)ORR by IRC, % (95% CI)95.8% (78.9, 99.9)85.4% (70.8, 94.4)Complete response, n (%)5 (20.8)5 (12.2)Partial response, n (%)18 (75.0)30 (73.2)Stable disease, n (%)1 (4.2)6 (14.6)Progressive disease, n (%)0 (0.0)0 (0.0)Not evaluable (NE), n (%)0 (0.0)0 (0.0)PFS by IRCMedian PFS, months (95% CI)NE (44.2, NE)27.4 (14.5, NE)Censored, %21 (87.5)24 (58.5)PFS rate at 24 months, % (95% CI)95.2 (70.7, 99.3)57.1 (38.6, 71.8)Median f/u, month24.930.4DoR by IRCMedian DoR, months (95% CI)NE (42.8, NE)26.7 (12.1, NE)Censored, %21 (91.3)20 (57.1)DoR rate at 24 months, % (95% CI)90.9 (50.8, 98.7)50.7 (30.4, 67.8)Median f/u, months17.833.9 Open table in a new tab NE; Not estimated. With longer f/u and additional pts, selpercatinib continues to demonstrate very durable responses in pts with RET-fusion thyroid cancer with or without prior therapy, suggesting use of selpercatinib as first systemic therapy appears to be highly effective in treatment of TC. The safety remained tolerable despite longer duration on treatment.