Aims
Selpercatinib is a highly selective oral RET inhibitor approved for treatment of RET-altered tumors in patients (pts) aged 12 years and older in Japan. We present final results from the LIBRETTO-121 study.
Methods
LIBRETTO-121 (NCT03899792) was a phase 1/2 trial in pts 0.5-21 yrs of age with advanced RET-altered solid tumors. Dosing started at 92 mg/m2 BID with no further escalation. Primary objectives were to evaluate safety and ORR (RECIST 1.1) by independent review committee (IRC).
Results
As of November 8, 2024, 36 pts aged 2-20 yrs were treated with selpercatinib, including 10 (27.8%) Asian pts. Tumor types were RET-mutant medullary thyroid cancer (n=15), RET fusion-positive papillary thyroid cancer (n=15), and other (n=6). Pts (n=36) treated with selpercatinib 92 mg/m2 (up to 160 mg BID) had a similar exposure as adults (n=667) treated with 160 mg BID at steady state on cycle 1 day 8. Time on selpercatinib was 0.4-62.4 mo; 25 pts remain on treatment. There were no DLTs or treatment discontinuations due to TEAEs. TEAEs of G3 or above included weight gain (11%), elevated ALT (8%), vomiting (8%), and anemia, constipation, hypertension, hypokalemia, and reduced neutrophil count (6% each). ORR (IRC) was 52.8% (19/36); 19.4% (7/36) had stable disease (CBR: 77.8% [28/36]). At 24 mo, the DOR was 100% (95% CI: 100, 100), and PFS rate was 86% (95% CI: 69%, 94%; mPFS: not reached; median follow-up: 30 mo).
Conclusions
Selpercatinib continues to show durable efficacy in pediatric and adolescent pts with RET-altered thyroid cancer and is tolerated with manageable toxicities.