Nuvalent, Inc. (Nasdaq: NUVL) announced it will host a webcast and conference call on Tuesday, June 24, 2025 at 8:00 a.m. ET, to discuss pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI pre-treated patients with advanced ROS1-positive non-small cell lung cancer from the global ARROS-1 Phase 1/2 clinical trial.
Novel ROS1 Inhibitor Addresses Treatment Resistance
Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. The drug is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R.
The investigational therapy is specifically designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. These characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy.
Regulatory Recognition and Trial Design
Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC.
The drug is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. The completed Phase 1 portion enrolled ROS1-positive NSCLC patients who previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors who had been previously treated.
Trial Objectives and Structure
The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of zidesamtinib, with additional objectives including determination of the recommended Phase 2 dose, characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity.
The ongoing global, single arm, open label Phase 2 portion is designed with registrational intent for TKI-naïve and TKI pre-treated patients with ROS1-positive NSCLC.
Company Focus on Precision Oncology
Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, the company develops innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses.
Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.
