Lilly's Retevmo Shows Significant Event-Free Survival Benefit in Early-Stage RET Fusion-Positive Lung Cancer
Key Insights
Eli Lilly's Retevmo (selpercatinib) demonstrated a highly statistically significant and clinically meaningful improvement in event-free survival as adjuvant therapy in the Phase 3 LIBRETTO-432 trial for early-stage RET (search) fusion-positive NSCLC.
The study met its primary endpoint in patients with stage II-IIIA disease following radiotherapy or surgery, marking the first randomized Phase 3 trial of a selective RET (search) kinase inhibitor in this adjuvant setting.
Overall survival results trended in favor of selpercatinib but were immature at the time of analysis, with the safety profile remaining consistent with previous trials.
Eli Lilly and Company announced positive topline results from the Phase 3 LIBRETTO-432 clinical trial, demonstrating that Retevmo (selpercatinib) delivered substantial event-free survival benefits as adjuvant therapy in patients with early-stage rearranged during transfection (RET (search)) fusion-positive non-small cell lung cancer (NSCLC). The study met its primary endpoint, showing a highly statistically significant and clinically meaningful improvement in investigator-assessed event-free survival compared to placebo.
First-in-Class Adjuvant Trial Results
LIBRETTO-432 represents the first and only randomized Phase 3 study to evaluate the safety and efficacy of a selective RET (search) kinase inhibitor as adjuvant therapy in this patient population. The trial enrolled 151 patients with stage II-IIIA RET fusion-positive NSCLC who were randomized 1:1 to receive either selpercatinib or placebo following completion of definitive radiotherapy or surgery with curative intent.
"We have consistently observed that cancer medicines can deliver their greatest impact when administered early in the course of a patient's treatment journey," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "The LIBRETTO-432 results support this observation, demonstrating an effect size in line with the most striking data for targeted adjuvant therapy in lung cancer."
Clinical Context and Patient Population
NSCLC accounts for approximately 85 percent of all lung cancer diagnoses in the United States, with around 30 percent of patients presenting with stage IB-IIIA disease. RET (search) fusions have been identified in one to two percent of all NSCLC cases, representing a specific molecular subset that can benefit from targeted therapy. Approximately 50 percent of people with NSCLC have actionable biomarkers, highlighting the importance of comprehensive genomic testing.
The primary endpoint focused on event-free survival as assessed by investigator in patients with stage II-IIIA RET (search) fusion-positive NSCLC. Secondary endpoints included overall survival, time to distant disease recurrence in the central nervous system, and safety parameters.
Safety Profile and Overall Survival Trends
Overall survival results trended in favor of selpercatinib, but were immature at the time of this analysis with few events observed. The overall safety profile of selpercatinib in LIBRETTO-432 was generally consistent with previously reported trials in the selpercatinib development program.
Van Naarden emphasized the broader implications for genomic testing, stating that "building on the adoption of targeted therapies for early-stage patients with EGFR- and ALK-driven lung cancer, we hope these results further accelerate the use of genomic testing for all people diagnosed with early-stage disease."
Regulatory and Development Context
Retevmo received FDA accelerated approval for metastatic RET (search) fusion-positive NSCLC in 2020, followed by full approval in 2022, both based on the phase 1/2 Libretto-001 study. The drug was acquired through Lilly's $8 billion purchase of Loxo in 2019.
Detailed results from LIBRETTO-432 will be presented at an upcoming medical congress, submitted to a peer-reviewed journal, and discussed with health authorities globally. The company plans to pursue regulatory discussions based on these positive adjuvant therapy results.