Nuvalent: rolling NDA submission for zidesamtinib initiated

Nuvalent: rolling NDA submission for zidesamtinib initiated

Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company, has announced the initiation of a rolling New Drug Application (NDA) submission for zidesamtinib in TKI (tyrosine kinase inhibitor) pre-treated advanced ROS1-positive non-small cell lung cancer (NSCLC) under the FDA's Real-Time Oncology Review (RTOR) program. The company presented pivotal data for zidesamtinib at the IASLC 2025 World Conference on Lung Cancer (WCLC 2025) in Barcelona, Spain, on September 7, 2025 [1].

The rolling NDA submission is based on data from Nuvalent's global ARROS-1 Phase 1/2 clinical trial, which included TKI pre-treated patients with advanced ROS1-positive NSCLC. The FDA has agreed to accept the NDA for participation in the RTOR program, allowing for the earlier submission of topline efficacy and safety results. Nuvalent aims to complete its rolling NDA submission in the third quarter of 2025 and is engaging with the FDA on potential opportunities for line-agnostic expansion [1].

Zidesamtinib is a novel, brain-penetrant ROS1-selective inhibitor designed to overcome limitations observed with currently available ROS1 inhibitors. It is intended for patients with ROS1-positive NSCLC who have developed resistance to existing TKIs or have brain metastases. Zidesamtinib has received breakthrough therapy designation and orphan drug designation for ROS1-positive NSCLC [1].

The ARROS-1 trial (NCT05118789) is a first-in-human Phase 1/2 clinical trial that enrolled ROS1-positive NSCLC patients who had previously received at least one ROS1 TKI. The Phase 1 portion of the trial evaluated the overall safety and tolerability of zidesamtinib, while the ongoing Phase 2 portion is designed with registrational intent for TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC [1].

Nuvalent's pipeline includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, as well as multiple discovery-stage research programs. The company's focus is on creating precisely targeted therapies for clinically proven kinase targets in cancer [1].

References:
[1] https://markets.ft.com/data/announce/detail?dockey=600-202509070445PR_NEWS_USPRX____NE67220-1