Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study

Xiangqian Zheng, Qinghai Ji, Yuping Sun, Minghua Ge, Bin Zhang, Ying Cheng, Shangtong Lei, Feng Shi, Ye Guo, Linfa Li, Lu Chen, Jingxin Shao, Wanli Zhang, Ming Gao, Xiangqian Zheng, Qinghai Ji, Yuping Sun, Minghua Ge, Bin Zhang, Ying Cheng, Shangtong Lei, Feng Shi, Ye Guo, Linfa Li, Lu Chen, Jingxin Shao, Wanli Zhang, Ming Gao

Abstract

Background: Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced RET-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 RET 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 RET fusion-positive TC or RET-mutant medullary TC (MTC) confirmed by central laboratory] and all enrolled patients with MTC.

Results: Of 77 enrolled patients, 29 had RET-mutant MTC and one had RET fusion-positive TC. In the PAS (n = 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 (n = 29), the ORR by IRC was 58.6% (95% CI, 38.9-76.5). One RET 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 (n = 77), 59.7% experienced grade ⩾3 treatment-emergent adverse events (TEAEs). TEAEs led to dose reductions in 32.5% (n = 25) and discontinuations in 5.2% [n = 4; 3.9% (n = 3) considered treatment related] of patients.

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

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

Keywords: Asian; RET fusion; RET kinase inhibitor; RET mutant; Selpercatinib; thyroid cancer.

Conflict of interest statement

Competing interests: Lu Chen, Jingxin Shao, and Wanli Zhang are employees of Eli Lilly and Company and receive a salary or stock share from Eli Lilly and Company. The other authors have no disclosures to make.

© The Author(s), 2022.

Figures

Figure 1.
Figure 1.
Antitumor activity of selpercatinib in patients withRET-mutant MTC. Waterfall plots of the best change in tumor size for (a) the PAS assessed by the IRC and (b) all enrolled patients with MTC. Each bar represents an individual patient. Notes: In the PAS (n = 26), one treatment-naïve patient with RET-mutant MTC did not have an evaluable response. Among all enrolled patients with MTC (n = 29), one patient did not have an evaluable response and one had only non-target lesions. IRC, independent review committee; MTC, medullary thyroid cancer; PAS, primary analysis set; RET, REarranged during Transfection.
Figure 2.
Figure 2.
DoR in patients with RET-mutant MTC. Kaplan–Meier estimates of DoR in (a) the PAS and (b) all patients with MTC who had CR or PR confirmed by IRC. CR, complete response; DoR, duration of response; IRC, independent review committee; MTC, medullary thyroid cancer; NR, not reached; PR, partial response; PAS, primary analysis set; RET, REarranged during Transfection.
Figure 3.
Figure 3.
Biochemical responses in patients with RET-mutant MTC included in the PAS: (a) calcitonin and (b) CEA. *Biochemical response evaluable populations comprisedRET-mutant MTC patients in the PAS with abnormal baseline levels of calcitonin or CEA, respectively $CR was defined as normalization of serum levels following treatment; PR was ⩾ 50% decrease from baseline serum levels; SD was between +50% and −50% change from baseline serum levels; progressive disease was ⩾ 50% increase from baseline serum levels; maintained for a minimum of 4 weeks. Objective biochemical response rate was defined as the proportion of patients achieving a complete or partial biochemical response. CI was calculated using the Clopper–Pearson method. CEA, carcinoembryonic antigen; CI, confidence interval; CR, complete response; MTC, medullary thyroid cancer; PAS, primary analysis set; PR, partial response; RET, REarranged during Transfection; SD, stable disease.

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