Retevmo demonstrates superior progression-free survival compared to approved multikinase inhibitors in RET-mutant medullary thyroid cancer

The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This result was based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee (IDMC). Adverse events observed on Retevmo were generally consistent with those identified across the previously reported Retevmo development program (LIBRETTO-001, LIBRETTO-121, LIBRETTO-321).

The labeling for Retevmo contains warnings and precautions for hepatotoxicity (evidence of liver dysfunction), interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryo-fetal toxicity.

"These data from the LIBRETTO-531 trial confirm the importance of selectivity in targeting RET-driven cancers and suggest Retevmo should be considered the preferred first-line treatment for people with advanced RET-mutant medullary thyroid cancer," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Taken together with the recent positive Retevmo Phase III LIBRETTO-431 announcement in lung cancer, these results underscore the importance of timely and broad-based genomic testing to ensure patients who could potentially benefit receive targeted therapies. We look forward to sharing detailed data with the oncology community."

LIBRETTO-531 is a Phase III, randomized, open-label trial evaluating Retevmo versus cabozantinib or vandetanib, which are currently approved first-line options for patients with advanced MTC. LIBRETTO-531 is the first randomized trial comparing the safety and effectiveness of a highly selective RET-kinase inhibitor versus multikinase inhibitors in this population. These results further build on the data from LIBRETTO-001, the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor, which includes more than 800 patients and spans 16 countries and 85 sites. In this trial, Retevmo demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers.

MTC accounts for 1–2 percent of thyroid cancers in the U.S. RET mutations are found in approximately 60 percent of sporadic MTC and over 90 percent of hereditary MTC.

Full results from the LIBRETTO-531 trial will be presented at an upcoming medical meeting, submitted to a peer-reviewed journal, and discussed with health authorities.

About LIBRETTO-531: LIBRETTO-531 is a randomized Phase III clinical trial of patients with progressive, advanced kinase inhibitor naïve RET-mutant MTC. The trial enrolled 291 patients and participants were randomized 2:1 to receive either selpercatinib or physician's choice of cabozantinib or vandetanib as initial treatment of their advanced RET-mutant MTC. RET mutations may be identified using local testing. This trial's primary endpoint is progression-free survival (PFS), and secondary endpoints include treatment failure-free survival (TFFS), overall response rate (ORR), duration of response (DoR), and overall survival (OS). For patients randomized to the control arm, crossover was allowed at progression.