Lilly's Retevmo Shows Significant Event-Free Survival Benefit in Early-Stage Lung Cancer Trial

Eli Lilly and Company announced positive topline results from the Phase 3 LIBRETTO-432 clinical trial of Retevmo (selpercatinib) as adjuvant therapy versus placebo. The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in investigator-assessed event-free survival (EFS) in patients with early-stage (II-IIIA) rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC).

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.

Detailed results will be presented at an upcoming medical congress, submitted to a peer-reviewed journal, and discussed with health authorities globally.

The executive vice president and president of Lilly Oncology stated that the LIBRETTO-432 results support the observation that cancer medicines can deliver their greatest impact when administered early in the course of a patient's treatment journey, demonstrating an effect size in line with the most striking data for targeted adjuvant therapy in lung cancer. Building on the adoption of targeted therapies for early-stage patients with EGFR- and ALK-driven lung cancer, the results are hoped to further accelerate the use of genomic testing for all people diagnosed with early-stage disease.

LIBRETTO-432 is the first and only randomized Phase 3 study to evaluate the safety and efficacy of a selective RET kinase inhibitor as adjuvant therapy in this population.

LIBRETTO-432 is a Phase 3, global, multicenter, randomized, double-blind, controlled clinical trial of selpercatinib versus placebo in patients with RET fusion-positive NSCLC following completion of definitive radiotherapy or surgery with curative intent, and other adjuvant therapy, if indicated. The trial enrolled 151 patients who were randomized 1:1 to receive either selpercatinib or placebo as adjuvant therapy for RET fusion-positive NSCLC. The primary endpoint is EFS as assessed by investigator in the primary analysis population, which was comprised of patients with stage II-IIIA RET fusion-positive NSCLC. Secondary endpoints include EFS as assessed by investigator in the overall population, overall survival (OS), EFS as assessed by blinded independent central review (BICR), time to distant disease recurrence in the central nervous system (CNS) as assessed by investigator and BICR, progression-free survival on the next line of treatment (PFS2), positive predictive value (PPV) of RET tests from investigator-identified laboratories with respect to the Lilly-designated RET test, safety and tolerability.

NSCLC accounts for about 85 percent of all lung cancer diagnoses in the U.S., and around 30 percent of patients with NSCLC present with stage IB-IIIA disease. Approximately 50 percent of people with NSCLC have actionable biomarkers, and RET fusions have been identified in one to two percent of all NSCLC cases.

Retevmo (selpercatinib), formerly known as LOXO-292, is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (less than 50 kg or 50 kg or greater, respectively), taken twice daily until disease progression or unacceptable toxicity.

Retevmo is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test.