Phase 3 Retevmo study produces topline results for patients with advanced or metastatic RET fusion-positive NSCLC

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In August 2023, Eli Lilly and Company announced favorable results from its recent LIBRETTO-431 study. The phase 3, randomized, open-label trial evaluated Retevmo (selpercatinib) versus platinum-based chemotherapy (cisplatin or carboplatin) plus pemetrexed with or without pembrolizumab. The latter is the current initial treatment for patients who have rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC).

LIBRETTO-431 is the first randomized trial that compares the targeted therapy’s safety and efficacy to that of a PD-1 inhibitor plus chemotherapy in a biomarker selected patient population. Having met its primary endpoint, the study demonstrated clinically meaningful and statistically significant improvement in progression-free survival (PFS). 

“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, MD, 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.”

The medical trial included 261 patients who have treatment-resistant RET with fusion-positive advanced or metastatic NSCLC. Participants received either Retevmo or platinum-based chemotherapy plus pemetrexed with or without pembrolizumab in a randomized 2:1 ratio.

Topline results and adverse outcomes from the phase 3 study were in line with those that have been identified and reported throughout the full Retevmo development program.  LIBRETTO-001, in particular, is the largest clinical trial to assess RET inhibitor treatment for patients with RET-driven cancers. It includes a phase 1 dose escalation and phase 2 dose expansion. The study produced strong and significant outcomes across a variety of tumor types.

Retevmo is an FDA-approved oral prescription drug that can affect both healthy and tumor cells, possibly resulting in side effects. Therefore, the medicine contains the following warning labels and precautions:

·      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

·      Embryo-fetal toxicity

Lilly will publish the complete results of the LIBRETTO-431 study in a peer-reviewed journal and present them at an upcoming medical meeting. 

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