Eli Lilly and Company (NYSE:LLY) announced positive data from its Phase 3 LIBRETTO-432 trial, showing that Retevmo significantly lowered the risk of disease recurrence or death in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC) following initial treatment.
The study found that treatment with Retevmo (selpercatinib) reduced the risk of recurrence or death by 83% compared with placebo, highlighting the drug’s potential role as an adjuvant therapy for patients with RET-driven lung cancer.
Trial Assessed Retevmo Following Surgery or Radiation
The LIBRETTO-432 trial enrolled 151 patients with stage IB to IIIA RET fusion-positive NSCLC who had previously undergone surgery or radiation therapy.
Participants were randomly assigned to receive either selpercatinib at a dose of 160mg twice daily or a placebo, with treatment continuing for up to three years.
The objective was to determine whether Retevmo could improve outcomes by reducing the likelihood of disease recurrence after initial treatment.
Event-Free Survival Significantly Improved
The primary analysis focused on 109 patients with stage II to IIIA disease and demonstrated a substantial benefit for those receiving selpercatinib.
Investigator-assessed event-free survival strongly favored the treatment group, with a hazard ratio of 0.17.
After a median follow-up period of 24 months, the event-free survival rate at two years reached 92% among patients treated with Retevmo, compared with 61% for those receiving placebo.
Median event-free survival had not yet been reached in the selpercatinib group at the time of analysis, whereas patients in the placebo arm recorded a median event-free survival of 31.8 months.
Safety Profile Remained Manageable
The safety findings were broadly consistent with the known profile of the drug.
Among adverse events classified as Grade 3 or higher, increased alanine aminotransferase levels were reported in 17% of patients receiving selpercatinib, compared with 1% in the placebo group.
Elevated aspartate aminotransferase levels occurred in 19% of patients treated with Retevmo, versus 3% among placebo recipients.
According to Lilly, these side effects were manageable through dose adjustments and treatment modifications.
Findings to Be Presented at ASCO and Published in Medical Journal
The company said the results will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and published simultaneously in the New England Journal of Medicine.
The trial represents the first randomized Phase 3 study to investigate a selective RET kinase inhibitor as adjuvant therapy for patients with RET fusion-positive NSCLC.
Lilly Preparing Regulatory Submissions
Following the positive outcome of LIBRETTO-432, Lilly intends to submit the data package to health regulators around the world for review.
If approved, Retevmo could become an important treatment option for patients with early-stage RET fusion-positive lung cancer, potentially helping to reduce the risk of recurrence after surgery or radiation therapy and improving long-term outcomes in this genetically defined patient population.