On August 13, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI (tyrosine kinase inhibitor) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from the global ARROS-1 Phase 1/2 clinical trial, in addition to preliminary data for TKI-naïve patients, will be presented as part of the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer (WCLC 2025) (Press release, Nuvalent, AUG 13, 2025, View Source [SID1234655215]). The conference is hosted by the International Association for the Study of Lung Cancer and is being held September 6-9, 2025, in Barcelona, Spain.
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"Since the inception of our ROS1 research program, collaboration with physician-scientists has been central to understanding the specific opportunities for a new therapeutic option to make a meaningful impact for patients living with ROS1-positive NSCLC. This collaboration helped to shape our vision for a future where physicians and their patients facing their next treatment decision do not have to choose between tolerability and efficacy," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "We are highly encouraged by these pivotal results for zidesamtinib in a TKI pre-treated ROS1-positive NSCLC population as well as the preliminary results in a TKI-naïve population, and look forward to engaging with the global lung cancer community on this important milestone at WCLC."
Details of the presentation are as follows:
Title: Pivotal ARROS-1 efficacy and safety data: zidesamtinib in TKI pre-treated patients with advanced/metastatic ROS1+ NSCLC
Session: PL02 – Presidential Symposium 1
Session Date and Time: Sunday, September 7, 2025, 8:15 a.m. – 10:30 a.m. CEST
Presenting Author: Alexander Drilon, M.D. (Memorial Sloan Kettering Cancer Center, New York, USA)
The company has initiated its rolling NDA submission 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) pilot 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. Completion of the NDA submission is targeted for the third quarter of 2025, and the company continues to engage with the FDA on potential opportunities for line-agnostic expansion.
About Zidesamtinib and the ARROS-1 Phase 1/2 Clinical Trial
Zidesamtinib is an investigational, 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.