The Phase 3 LIBRETTO-432 trial evaluated Retevmo as adjuvant therapy in early-stage RET fusion-positive non-small cell lung cancer patients following surgical resection. The primary endpoint measured disease-free survival, demonstrating an 83% reduction in disease recurrence or death risk versus placebo. The hazard ratio supports a clinically meaningful benefit in this biomarker-defined population. This represents the first Phase 3 readout for a RET-selective inhibitor in adjuvant lung cancer.
Retevmo received FDA accelerated approval in May 2020 for RET-altered cancers. The adjuvant indication requires a supplemental Biologics License Application under 21 CFR 314.71, supported by confirmatory Phase 3 data. The FDA previously granted Priority Review for the original application, suggesting expedited pathways may apply. EMA's CHMP issued a positive opinion under centralized marketing authorization in February 2021. Lilly must submit LIBRETTO-432 data to both agencies within standard reporting timelines.
The adjuvant setting represents a competitive frontier where Roche's Alecensa and Pfizer's Lorbrena have established precedents in ALK-positive disease. Retevmo's 83% risk reduction creates a new benchmark for biomarker-driven adjuvant therapy in RET fusion-positive lung cancer. Approximately 1-2% of NSCLC patients harbor RET fusions, translating to a defined eligible population. Lilly anticipates filing the sBLA by Q4 2026, with potential FDA action by mid-2027.