On September 7, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported 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 (Press release, Nuvalent, SEP 7, 2025, View Source [SID1234655805]). The presentation slides will be available on the Nuvalent website at www.nuvalent.com following the Presidential Symposium.
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The pivotal data presented today, initially announced in June 2025, serve as the foundation for the company’s ongoing rolling New Drug Application (NDA) submission to the U.S. 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 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.
"There remains a clear need for new treatment options for patients with ROS1-positive NSCLC, particularly those who are unable to tolerate the currently available TKIs, and those whose disease progresses with brain metastases or resistance mutations," said Christopher Turner, M.D., Chief Medical Officer at Nuvalent. "We are encouraged by the data presented today, which we believe highlight the potential of zidesamtinib to deliver meaningful outcomes with a generally safe and well-tolerated safety profile. These data represent important progress toward our goal of offering a new standard of care for this patient community. Congratulations to the entire Nuvalent team and our collaborators for the achievement of this important milestone."
About Zidesamtinib and the ARROS-1 Phase 1/2 Clinical Trial
Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib 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. In addition, zidesamtinib is 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. Together, 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. 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 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. 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), 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 advanced ROS1-positive NSCLC.