On Sunday, Nuvalent Inc (Nasdaq: NUVL), a US-based clinical-stage biopharmaceutical company involved in therapies for clinically proven kinase targets in cancer, presented on pivotal data for zidesamtinib, a novel investigational ROS1-selective inhibitor, in TKI (tyrosine kinase inhibitor) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from its global ARROS-1 Phase 1/2 clinical trial as part of the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer (WCLC 2025), being held in Barcelona, Spain.

Presentation slides will be available on the Nuvalent website at www.nuvalent.com following the Presidential Symposium.

The pivotal data presented, which was initially announced in June 2025, serve as the foundation for the company's ongoing rolling New Drug Application (NDA) submission to the US Food and Drug Administration (FDA) for zidesamtinib in TKI pre-treated patients with advanced ROS1-positive NSCLC. The FDA agreed to accept the NDA for participation in the Real-Time Oncology Review (RTOR) program, which facilitates earlier submission of topline efficacy and safety results prior to the submission of the complete application, to support an earlier start to the FDA's evaluation of the application. The company says that it is on track to complete its rolling NDA submission in the third quarter of 2025, and continues to engage with the FDA on potential opportunities for line-agnostic expansion.

According to the company, zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumours that have developed resistance to currently available ROS1 inhibitors, including tumours with treatment-emergent ROS1 mutations such as G2032R. 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.

Zidesamtinib 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 tumours. 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 tumours who had been previously treated. 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 (RP2D), characterisation of the pharmacokinetic profile, and evaluation of preliminary anti-tumour 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 advanced ROS1-positive NSCLC.