China-based ScinnoHub Pharmaceutical Co., Ltd. has initiated a first-in-human Phase I trial of SNH-118110, an oral small-molecule RET inhibitor, in patients with advanced RET-altered solid tumors. The trial's design — which includes a dedicated cohort for patients who have already progressed on a selective RET inhibitor — signals that ScinnoHub is positioning SNH-118110 as a next-generation agent intended to address acquired resistance to selpercatinib (Retevmo) and pralsetinib (Gavreto), the two approved agents that currently define the standard of care in this setting.
The open-label, multicenter Phase I study (NCT07649200) will enroll approximately 240 adults across dose-escalation and dose-expansion stages. The escalation phase admits patients with any RET-altered advanced solid tumor who have exhausted standard options; the expansion phase then stratifies into three cohorts: RET fusion-positive non-small cell lung cancer (NSCLC) after at least one prior RET inhibitor, treatment-naive RET fusion-positive NSCLC, and other RET-altered solid tumors including medullary thyroid cancer. Enrollment is set to begin in Q2 2026 at the East Hospital Affiliated to Tongji University in Shanghai, with primary completion anticipated by Q2 2027. The primary endpoints are safety and determination of the maximum tolerated dose or maximum administered dose; secondary measures include objective response rate, progression-free survival, duration of response, and pharmacokinetic parameters. The trial identifier is NCT07649200.
RET fusions and activating point mutations occur in approximately 1–2% of NSCLC cases and in the majority of hereditary medullary thyroid cancers, providing a defined biomarker-selected population. Selpercatinib and pralsetinib demonstrated durable responses in these patients, but resistance emerges — commonly through secondary RET kinase domain mutations such as G810X — for which no approved salvage option currently exists.