LIBRETTO-001-BTC

NCT03157128 📎

Regimen

Experimental
Selpercatinib 160 mg PO BID (continuous) — selective RET inhibitor with CNS penetrance
Control
single-arm / no comparator

Population

RET fusion-positive advanced solid tumors excluding lung and thyroid (those had dedicated larger LIBRETTO-001 cohorts); pan-tumor basket n=45 (Subbiah V, Lancet Oncol 2022). BTC/CCA subgroup: n=7 of 45 non-lung/non-thyroid patients; RET fusions occur in <1% BTC. RET fusion detected by RNA-based NGS or DNA NGS. Selpercatinib received FDA tumor-agnostic approval for RET fusion-positive solid tumors (September 2022).

Key finding

Selpercatinib demonstrated durable responses (median DoR 24.5 mo) in RET fusion-positive non-lung/non-thyroid tumors, supporting tumor-agnostic FDA approval. The BTC subgroup (n=7) showed ORR consistent with the overall cohort, though the ultra-small N precludes definitive BTC-specific conclusions. RET fusions in BTC are very rare (<1%), detectable by comprehensive NGS panels; when present, they represent a highly actionable target given the strong efficacy signal from the broader RET fusion evidence base. CNS activity of selpercatinib is relevant if BTC patients have brain metastases.

Source: PMID 36108661

Timeline

    Guideline citations

    • NCCN BTC (p.40)