LIBRETTO-432 Trial in Progress: A Phase 3 study of adjuvant selpercatinib or placebo in Stage IB-IIIA Ret fusion-positive (RET+) NSCLC

Around 30% of NSCLC patients (pts) present with stage IB-IIIA disease. Recent Phase III trial data suggest the potential for benefit for pts treated with targeted therapies in the adjuvant setting for stage IB-IIIA (ADAURA and ALINA). RET, an oncogenic driver in NSCLC is a promising target. Selpercatinib, a potent RET inhibitor, demonstrated longer PFS than platinum-based chemotherapy as 1L treatment in pts with RET+advanced NSCLC (Zhou et al. NEJM 2023). LIBRETTO-432 is a Phase 3, global trial evaluating efficacy and safety of adjuvant selpercatinib v Placebo in RET+Stage IB-IIIA NSCLC (NCT04819100).

Pts (n≈170) will be randomized (1:1) to selpercatinib BID [160mg≥50kg; 120mg<50kg], or Placebo, in continuous 28-day cycles for 3y. Stratification factors include disease stage (IB/II/IIIA) and prior definitive therapy (surgery/radiation+/- neo-adjuvant therapy). Treatment will continue until disease recurrence/progression, unacceptable toxicity. Crossover is allowed for Placebo pts who experience disease recurrence/progression. Eligible pts include:≥18y; histologically confirmed Stage IB/II/IIIA NSCLC; RET+tumor; have undergone prior definitive locoregional therapy with curative intent. Maximum time from therapy completion to randomization is 26w. Key exclusions are other oncogenic drivers; SCLC; and disease recurrence/progression post definitive therapy. Primary endpoint is investigator-assessed event-free survival (IAEFS) in the primary analysis population (pts with Stage II-IIIA). EFS is time from randomization until locoregional disease recurrence with histopathological confirmation, metastatic disease recurrence, or death. Gated secondary endpoints include IAEFS in the overall population (including Stage 1B pts) and OS in both primary analysis and overall populations. Recruitment is ongoing, with enrollment across ~170 sites and 30 countries. Results from this trial will further inform the value of RET inhibition and genomic testing for adjuvant NSCLC pts.

Publication History

Article published online:
18 March 2025