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. 2022 Sep;18(28):3143-3150.
doi: 10.2217/fon-2022-0657. Epub 2022 Aug 15.

LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer

Lori J Wirth  1 , Marcia S Brose  2 , Rossella Elisei  3 , Jaume Capdevila  4 , Ana O Hoff  5 , Mimi I Hu  6 , Makoto Tahara  7 , Bruce Robinson  8 , Ming Gao  9 , Meng Xia  10 , Patricia Maeda  10 , Eric Sherman  11
Affiliations

LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer

Lori J Wirth et al. Future Oncol. 2022 Sep.

Abstract

Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. Key secondary objectives are to compare other efficacy outcomes (per RECIST 1.1) and tolerability of selpercatinib versus cabozantinib or vandetanib.

Keywords: RET alteration; RET kinase inhibitor; RET mutation; medullary thyroid cancer; phase III trial; selpercatinib; targeted therapy.

Plain language summary

Selpercatinib (also known by the brand name Retevmo®/Retsevmo®) is a new treatment available in multiple countries for people with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). Thyroid cancer starts in your thyroid gland and may spread or metastasize to other parts of the body, including lungs, bones, and occasionally the brain, which means the cancer is likely to be advanced. Advanced thyroid cancer can be driven by a gene in your body, one of which is RET. This is a summary of the LIBRETTO-531 study which compares selpercatinib, which is a strong and selective inhibitor of RET, with two approved drugs, cabozantinib and vandetanib. Patients with advanced or metastatic RET-mutant MTC who have not already received treatment with kinase inhibitors are being enrolled. This trial will evaluate how long people during and after treatment live with the disease without it getting worse. Selpercatinib may affect both healthy cells and tumor cells, which can result in side effects, which will also be evaluated in this study. This study is active and currently recruiting new patients. Clinical Trial Registration: NCT04211337 (ClinicalTrials.gov).

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. LIBRETTO-531 study design.
BICR: Blinded independent committee review; BID: Twice daily; DOR: Duration of response; MKI: Mulitkinase inhibitor; ORR: Objective response rate; OS: Overall survival; PD: Progressive disease; PFS: Progression-free survival; PFS2: Progression after the next line of therapy; QD: Once daily; RECIST 1.1: Response Evaluation Criteria in Solid Tumors version 1.1; TFFS: Treatment failure free survival, which incorporates radiographic PD, unacceptable toxicity (predefined by protocol) or death.
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