OncoMatch/Clinical Trials/Repotrectinib

Repotrectinib (Augtyro) Clinical Trials

Repotrectinib (Augtyro, TPX-0005) is a next-generation, macrocyclic ROS1 and TRK inhibitor FDA-approved for ROS1-positive metastatic NSCLC (November 2023) and, under accelerated approval, for NTRK fusion-positive solid tumors (June 2024). Its compact macrocyclic structure is designed to maintain potency against resistance mutations — including the ROS1 G2032R solvent-front mutation — that limit the durability of earlier-generation agents such as crizotinib (first-generation) and entrectinib (second-generation). In the TRIDENT-1 trial, repotrectinib achieved objective response rates of approximately 79% in TKI-naive ROS1-positive NSCLC and 38% in patients with one prior ROS1 TKI, with demonstrated CNS activity. Repotrectinib is FDA-approved for ROS1-positive metastatic NSCLC and NTRK fusion-positive solid tumors (tumor-agnostic, June 2024); active trials are evaluating earlier-line use, resistance settings, and combination strategies. Eligibility requires confirmed ROS1 fusion or NTRK1/2/3 fusion; prior TKI therapy and number of prior lines vary by cohort.