Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Event-free survival (EFS) with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive (RET+) NSCLC: primary results of the phase 3 LIBRETTO-432 trial (145923)

Jonathan Goldman 1 , Xue-Ning Yang 2 , Maximilian Hochmair 3 , Lin Wu 4 , Hye Ryun Kim 5 , Luis Paz-Ares 6 , Damian Tobias Rieke 7 , Melissa Johnson 8 , James Chih-Hsin Yang 9 , Masahiro Tsuboi 10 , Benjamin Besse 11 , Nivedita Sharma 12 , Patricia Maeda 12 , Patrick Peterson 12 , Bente Frimodt-Moller 13 , Yi Yang 14 , Alexander Drilon 15 , Yi-Long Wu 2 , Aarohan Pruthi 16
  1. University of California, Los Angeles, USA
  2. Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
  3. Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria
  4. Hunan Cancer Hospital, Hunan, China
  5. Yonsei University Cancer Center, Seoul, South Korea Republic
  6. Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain
  7. Charité - Universitätsmedizin Berlin, Berlin, Germany
  8. Sarah Cannon Research Institute, , Nashville, TN, USA
  9. National Taiwan University Cancer Center, Taipei, Taiwan
  10. National Cancer Center Hospital East, Kashiwa, Japan
  11. Paris Saclay University, Gustave Roussy, Villejuif, France
  12. Eli Lilly and Company, Indianapolis, IN, USA
  13. Eli Lilly and Company, Copenhagen, Denmark
  14. Department of Thoracic Surgery, the Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu , Chengdu, Sichuan, China
  15. MSKCC - Memorial Sloan Kettering Cancer Center, New York, NY, USA
  16. Eli Lilly, Sydney, NSW, Australia

Aims: Selpercatinib, a selective, potent and brain-penetrant RET inhibitor, is approved for RET+ advanced/metastatic non-small cell lung cancer (NSCLC). We report the efficacy and safety of selpercatinib vs placebo in patients with stage IB-IIIA RET+ NSCLC. 

Methods: LIBRETTO-432 is a placebo-controlled, double-blind, phase 3 randomized (1:1) trial of selpercatinib 160mg BID vs placebo for ≤3 years in patients with stage IB-IIIA RET+ NSCLC after definitive locoregional treatment. Primary endpoint was investigator-assessed EFS in stage II-IIIA patients.

Results: In total, 151 patients were randomized (selpercatinib n=75; placebo n=76). Median follow-up was 24 months for selpercatinib and 27 months for placebo. At the preplanned efficacy analysis, selpercatinib demonstrated significantly improved EFS in patients with stage II-IIIA disease (n=109), HR 0.172 (95%CI:0.058-0.509; p=0.0003). The median EFS was not reached for selpercatinib vs 31.8 months for placebo (4 vs 19 EFS events, respectively). EFS by BICR, HR=0.125 (95%CI:0.028-0.552), was consistent with investigator-assessed EFS. The 2-year EFS rate was 91.5% for selpercatinib vs 61.1% for placebo. In the overall population (n=151), error-controlled EFS HR=0.165 (95%CI:0.056-0.485; p=0.0002), and median EFS was not reached on either treatment arm. Most common AEs were increased ALT/AST. Only 3 deaths were observed, all in the placebo arm. No patients died during assigned study treatment.

Conclusions: Selpercatinib achieved a statistically significant and clinically meaningful improvement in EFS vs placebo in patients with early-stage RET+ NSCLC. These data add to the body of evidence for targeted therapy in the adjuvant NSCLC setting and underscore the importance of comprehensive genomic testing at diagnosis of NSCLC.