Retevmo is the first targeted therapy to demonstrate superior progression-free survival compared to a PD-1 inhibitor for newly-diagnosed advanced RET Fusion-positive non-small cell lung cancer.- Eli Lilly

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.

LIBRETTO-431 is a Phase III, randomized, open-label trial evaluating Retevmo versus platinum-based chemotherapy (cisplatin or carboplatin) plus pemetrexed with or without pembrolizumab, which is a current first-line standard of care option for patients with EGFR/ALK-negative NSCLC. LIBRETTO-431 is the first randomized trial comparing the safety and effectiveness of a targeted therapy to a PD-1 inhibitor plus chemotherapy in a biomarker selected patient population.

"The LIBRETTO-431 trial aims to answer an important question about the selection of initial treatment for people with advanced RET fusion-positive NSCLC and these results suggest Retevmo should be considered a first-line standard of care," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Additionally, this clinically meaningful achievement of improved outcomes underscores the importance of timely and comprehensive genomic testing to inform initial treatment decisions for all patients with NSCLC. The results of this study provide further confirmation that RET status – like EGFR, ALK, and others in the family of lung cancer oncogenic drivers – should be known prior to initiating therapy. We look forward to sharing these data in more detail with the oncology community."

These results build on the data from LIBRETTO-001, the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor , which spans 16 countries and 85 sites, and includes a dose escalation phase (Phase 1) and a dose expansion phase (Phase II). In this trial, Retevmo demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers.

NSCLC accounts for about 85 percent of all lung cancer diagnoses in the U.S., of which approximately 50 percent have actionable biomarkers. RET fusions have been identified in approximately one to two percent of all NSCLC cases. Full results from the LIBRETTO-431 trial will be presented at an upcoming medical meeting, submitted to a peer-reviewed journal, and discussed with health authorities.