Efficacy and Safety of Selpercatinib in Chinese Patients with Advanced -altered Thyroid Cancers: Results from the Phase II LIBRETTO-321 Study

Background: Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced -altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown.

Patients And Methods: In the open-label, multi-center phase II LIBRETTO-321 (NCT04280081) study, Chinese patients with advanced solid tumors harboring alterations received selpercatinib 160 mg twice daily. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR) and safety. Efficacy was assessed in the primary analysis set [PAS; treated patients with fusion-positive TC or mutant medullary TC (MTC) confirmed by central laboratory] and all enrolled patients with MTC.

Results: Of 77 enrolled patients, 29 had -mutant MTC and one had fusion-positive TC. In the PAS ( = 26), the ORR by IRC was 57.7% [95% confidence interval (CI), 36.9-76.6]. Median DoR was not reached and 93.3% of responses were ongoing at a median follow-up of 8.7 months. In all enrolled MTC patients ( = 29), the ORR by IRC was 58.6% (95% CI, 38.9-76.5). One fusion-positive TC patient treated for 23.4 weeks achieved a partial response at week 8 that was ongoing at cutoff. In the safety population ( = 77), 59.7% experienced grade ⩾3 treatment-emergent adverse events (TEAEs). TEAEs led to dose reductions in 32.5% ( = 25) and discontinuations in 5.2% [ = 4; 3.9% ( = 3) considered treatment related] of patients.

Conclusions: Selpercatinib showed robust antitumor activity and was well tolerated in Chinese patients with advanced -altered TC, consistent with global data from LIBRETTO-001 (NCT04280081).

Clinicaltrialsgov Identifier: NCT04280081 (first posted Feb 21, 2020).