Nuvalent Presents Pivotal Data for Zidesamtinib in Advanced ROS1-Positive NSCLC Patients

Nuvalent presented pivotal data for zidesamtinib, a ROS1-selective inhibitor, in TKI pre-treated patients with advanced ROS1-positive NSCLC from its ARROS-1 Phase 1/2 clinical trial. The data serve as the foundation for the company's ongoing rolling NDA submission to the FDA. The FDA has agreed to accept the NDA for participation in the RTOR program, facilitating earlier submission of efficacy and safety results. Nuvalent aims to complete the rolling NDA submission in Q3 2025 and engage with the FDA on potential line-agnostic expansion.

Nuvalent, Inc. (Nasdaq: NUVL) has presented pivotal data for its investigational ROS1-selective inhibitor, zidesamtinib, 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. The data, presented at the IASLC 2025 World Conference on Lung Cancer (WCLC 2025) in Barcelona, Spain, serve as the foundation for the company's ongoing rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) [1].

The FDA has agreed to accept the NDA for participation in the Real-Time Oncology Review (RTOR) program, which allows for the earlier submission of topline efficacy and safety results prior to the submission of the complete application. This program facilitates an earlier start to the FDA's evaluation of the application [1].

Nuvalent aims 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. The company is developing zidesamtinib to overcome limitations observed with currently available ROS1 inhibitors and to improve treatment options for patients with brain metastases or resistance mutations [1].

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. It is also 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 drive deep, durable responses for patients across all lines of therapy [1].

The ARROS-1 trial (NCT05118789) is 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 [1].

Nuvalent, a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, 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 [1].

References:
[1] https://www.marketscreener.com/news/nuvalent-presents-pivotal-data-from-arros-1-clinical-trial-of-zidesamtinib-for-tki-pre-treated-patients-with-advanced-ros1-positive-nsclc-ce7d59ded98df527