Lilly’s RET Kinase Inhibitor Retevmo Achieves Primary Endpoint in Phase 3 Trial, Significantly Improving PFS in Advanced Medullary Thyroid Cancer

▎WuXi

Edited by Kant Content Team

Eli Lilly and Company today announced the topline results of the Phase 3 LIBRETTO-531 trial, which evaluated the efficacy and safety of Retevmo compared to physician-choice multi-kinase inhibitors (MKIs) as an initial therapy for patients with advanced or metastatic medullary thyroid cancer (MTC) harboring RET mutations. The analysis showed that the study met its primary endpoint, demonstrating a statistically and clinically significant improvement in progression-free survival (PFS) for patients receiving Retevmo.According to the press release, LIBRETTO-531 is the first randomized trial comparing the safety and efficacy of a RET kinase inhibitor with a multi-kinase inhibitor in this patient population.

In the United States, MTC accounts for 1-2% of thyroid cancer cases, with RET mutations found in approximately 60% of sporadic MTC and over 90% of hereditary MTC.

Retevmo is a potent RET kinase inhibitor that received its first U.S. FDA approval in 2020.Accelerated Approval, treating three types of cancer: non-small cell lung cancer, medullary thyroid carcinoma, and thyroid cancer.These patients have fusions or mutations in the RET gene in their tumors. In September last year, the U.S. FDA granted accelerated approval to Retevmo's expanded indication application for the treatment of patients with locally advanced or metastatic solid tumors carrying RET gene fusions, regardless of cancer type.

LIBRETTO-531 is a randomized, open-label Phase 3 trial designed to evaluate the efficacy of Retevmo compared to cabozantinib or vandetanib, which are currently approved as first-line treatment options for patients with advanced MTC. The trial results are based on a pre-specified interim efficacy analysis conducted by an Independent Data Monitoring Committee (IDMC).Data show that Retevmo significantly improved PFS in patients compared to the active control group.The adverse events observed with Retevmo were generally consistent with the adverse events identified in previously reported Retevmo trials. Complete data will be presented at an upcoming medical conference and submitted to regulatory authorities.

This trial result is based on the data from LIBRETTO-001, a large clinical trial conducted in patients with RET-driven cancers treated with a RET inhibitor. The trial included more than 800 patients across 16 countries and regions and 85 research centers. In this trial, Retevmo demonstrated clinically meaningful and durable responses across various tumor types in patients with RET-driven cancers.

References:

[1] Lilly's Retevmo® (selpercatinib)Demonstrates Superior Progression-Free Survival Compared to ApprovedMultikinase Inhibitors in RET-Mutant Medullary Thyroid Cancer. Retrieved August22, 2023 from https://investor.lilly.com/news-releases/news-release-details/lillys-retevmor-selpercatinib-demonstrates-superior-progression