At a Glance
- LIBRETTO-432 met its primary endpoint, showing a statistically significant improvement in event-free survival
- Overall survival favored selpercatinib, though data remain immature
- Safety findings aligned with the known selpercatinib profile
- First randomized Phase 3 trial of a selective RET inhibitor in the adjuvant NSCLC setting
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company has reported positive topline results from the Phase 3 LIBRETTO-432 clinical trial evaluating Retevmo (selpercatinib) as adjuvant therapy in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC).
The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in investigator-assessed event-free survival (EFS) compared with placebo.
Overall survival data showed a favorable trend for selpercatinib, although the results remain immature due to a limited number of events at the time of analysis.
A Targeted Strategy in Early Disease
Selpercatinib is a highly selective RET kinase inhibitor designed to block oncogenic RET alterations, which are recognized drivers of tumor growth. The drug has previously demonstrated robust activity in advanced RET-altered cancers, including central nervous system (CNS) metastases.
LIBRETTO-432 extends this precision approach into the adjuvant setting, where treatment is administered following surgery or definitive radiotherapy with curative intent.
Inside the LIBRETTO-432 Trial
LIBRETTO-432 (NCT04819100) is a global, randomized, double-blind Phase 3 trial comparing selpercatinib with placebo in patients with RET fusion-positive NSCLC after completion of definitive therapy.
Key trial characteristics:
- Enrolment: 151 patients
- Randomization: 1:1 (selpercatinib vs placebo)
- Primary Endpoint: Investigator-assessed EFS in stage II–IIIA patients
- Secondary Endpoints: Overall survival, blinded independent central review (BICR) EFS, CNS recurrence, PFS2, safety, and diagnostic test performance.
The trial represents the first randomized Phase 3 study assessing a selective RET inhibitor as adjuvant therapy in this molecularly defined population.
Safety Profile Remains Consistent
Lilly stated that the overall safety findings were generally consistent with the known profile of selpercatinib observed in prior studies. No unexpected safety signals were reported.
Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, emphasized the importance of earlier intervention: Cancer therapies often achieve their greatest clinical impact when used early in the treatment course. The LIBRETTO-432 findings reinforce this principle and support expanding genomic testing in early-stage lung cancer.
Non-small cell lung cancer accounts for approximately 85 percent of lung cancer diagnoses in the United States. Around 30 percent of patients present with stage IB–IIIA disease, where curative treatment strategies are feasible.
While roughly half of NSCLC cases harbor actionable biomarkers, RET fusions occur in approximately one to two percent of patients. Despite their rarity, RET-driven tumors represent a clinically important subset due to the availability of targeted therapies.
The results add to a growing body of evidence supporting biomarker-guided adjuvant treatment, following similar advances in EGFR- and ALK-driven lung cancers.
Detailed trial results will be presented at an upcoming medical congress, submitted for peer-reviewed publication, and discussed with regulatory authorities worldwide.
Access the latest US FDA-approved full prescribing information (USPI) PDF here, which details adverse events (AEs), adverse drug reactions (ADRs), precautions, and warnings: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213246s011s013lbl.pdf.
Reference
Lilly’s Retevmo (selpercatinib) delivers substantial event-free survival benefit as an adjuvant therapy in early-stage RET fusion-positive lung cancer, 16 February 2026, Lilly’s Retevmo (selpercatinib) delivers substantial event-free survival benefit as an adjuvant therapy in early-stage RET fusion-positive lung cancer | Eli Lilly and Company
A Study of Selpercatinib After Surgery or Radiation in Participants with Non-Small Cell Lung Cancer (NSCLC) (LIBRETTO-432), ClinicalTrials.gov ID NCT04819100, https://clinicaltrials.gov/study/NCT04819100
Tsuboi M et al, LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer. Future Oncol. 2022 Sep;18(28):3133-3141. Epub 2022 Aug 11. PMID: 35950566. https://doi.org/10.2217/fon-2022-0656