35P Final data from phase I/II LIBRETTO-001 trial of selpercatinib in RET fusion-positive non-small cell lung cancer

Selpercatinib is a highly selective and potent CNS-active RET kinase inhibitor approved for the treatment of RET fusion-positive NSCLC based on the results of the phase I/II trial LIBRETTO-001 (NCT03157128). The final LIBRETTO-001 data for NSCLC is reported. Patients with advanced, RET fusion-positive (identified by NGS, PCR or FISH) NSCLC who were treatment naïve or who had previously received platinum-based chemotherapy were enrolled at a selpercatinib dose of 160 mg BID. The primary end point was objective response rate (ORR) by RECIST 1.1 assessed by an independent review committee. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. In 69 treatment naïve patients, the ORR was 83% with a mDoR of 20.3 mo (median follow-up 37.1 mo) and mPFS of 22.0 mo (Table). In 247 patients who had previously received platinum-based chemotherapy, the ORR was 62% with a mDoR of 31.6 mo (median follow-up 39.5 mo) and mPFS of 26.2 mo. Across both groups, 26 patients had measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-mDoR of 9.4 mo (median follow up 25.8 mo) and CNS-mPFS of 11.0 mo. At the 36 mo landmark estimate, 57% of previously treated patients and 66% of treatment naïve patients were alive. The overall safety profile was consistent with previous reports. The most common adverse events (AEs) ≥G3 in ≥10% patients were hypertension and increased AST/ALT. Dose reduction from any cause occurred in 53% of patients. In total 11% discontinued treatment due to AEs, including 4% due to AEs related to selpercatinib as assessed by the investigator.Table: 35PPreviously treated with platinum-based chemotherapy N=247Treatment naïve N=69ORR, % (95% CI)62 (55, 68)83 (72, 91)mTime to Response, mo1.91.8mDoR, mo (95% CI)31.6 (20.4, 42.3)20.3 (15.4, 29.5)Censoring, %49.343.9Median follow-up, mo39.537.136 mo DoR, %44.7 (35.7, 53.4)35.4 (22.0, 49.0)mPFS, mo (95% CI)26.2 (19.3, 35.7)22.0 (16.5, 24.9)Censoring, %46.244.9Median follow-up, mo41.238.936 mo PFS, %41.1 (34.2, 47.9)34.6 (22.3, 47.3)mOS, mo (95% CI)47.6 (35.9, NE)NE (37.8, NE)Censoring, %55.562.3Median follow-up, mo44.641.936 mo OS, %56.6 (49.8, 62.8)65.6 (52.4, 75.9) Open table in a new tab In the final analysis, selpercatinib continued to show durable responses and intracranial activity with a manageable safety profile in patients with RET fusion-positive NSCLC. These data and the recent positive results from the phase III trial LIBRETTO-431, reinforce the importance of genomic testing to identify RET fusions at initial diagnosis.