Nuvalent Initiates Rolling NDA Submission for Zidesamtinib in ROS1-Positive NSCLC Under RTOR Program.

Nuvalent has initiated a rolling New Drug Application (NDA) submission for zidesamtinib, a ROS1-selective inhibitor, in TKI pre-treated advanced ROS1-positive NSCLC under the FDA's Real-Time Oncology Review (RTOR) program. The submission is expected to complete in Q3 2025. Pivotal data from the ARROS-1 Phase 1/2 clinical trial was presented at the IASLC 2025 World Conference on Lung Cancer.

Nuvalent, Inc. (Nasdaq: NUVL) has initiated a rolling New Drug Application (NDA) submission for zidesamtinib, a ROS1-selective inhibitor, in TKI pre-treated advanced ROS1-positive non-small cell lung cancer (NSCLC) under the FDA's Real-Time Oncology Review (RTOR) program. The submission is expected to be completed by the end of the third quarter of 2025. Pivotal data from the ARROS-1 Phase 1/2 clinical trial was presented at the IASLC 2025 World Conference on Lung Cancer in Barcelona, Spain.

The data, initially announced in June 2025, highlights the potential of zidesamtinib to deliver meaningful outcomes with a generally safe and well-tolerated safety profile. Zidesamtinib is designed to overcome limitations observed with currently available ROS1 inhibitors, including resistance mutations and brain metastases. The drug is also designed to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family, which can lead to CNS adverse events seen with dual TRK/ROS1 inhibitors.

The ARROS-1 trial, which enrolled TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC, is designed with registrational intent. The Phase 1 portion of the trial evaluated the safety and tolerability of zidesamtinib, while the ongoing Phase 2 portion aims to further assess its efficacy and safety.

Nuvalent is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer. The company is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, among others.

The FDA's RTOR program facilitates earlier submission of topline efficacy and safety results prior to the submission of the complete application, potentially expediting the FDA's evaluation of the application. Nuvalent's submission is on track for completion by the end of the third quarter of 2025.

Nuvalent's Chief Medical Officer, Christopher Turner, M.D., stated that 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 or whose disease progresses with brain metastases or resistance mutations. The company is encouraged by the data presented, which highlight the potential of zidesamtinib to deliver meaningful outcomes.

References:
1. [Nuvalent presents pivotal data from ARROS-1 clinical trial of zidesamtinib for TKI pre-treated patients with advanced ROS1-positive NSCLC at WCLC 2025](https://markets.ft.com/data/announce/detail?dockey=600-202509070445PR_NEWS_USPRX____NE67220-1)
2. [Nuvalent presents pivotal data from ARROS-1 clinical trial of zidesamtinib for TKI pre-treated patients with advanced ROS1-positive NSCLC at WCLC 2025](https://www.marketscreener.com/news/nuvalent-presents-pivotal-data-from-arros-1-clinical-trial-of-zidesamtinib-for-tki-pre-treated-patie-ce7d59ded98df527)