Nuvalent(US:NUVL) Prnewswire·2025-06-24 10:30Core Insights - Nuvalent, Inc. announced positive pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from the global ARROS-1 Phase 1/2 clinical trial [1][2] Group 1: Clinical Trial Progress - The company completed a pre-New Drug Application (NDA) meeting with the FDA and plans to initiate a rolling NDA submission in July 2025, targeting completion in the third quarter of 2025 [2][4] - Zidesamtinib demonstrated an overall response rate (ORR) of 44% in 117 TKI pre-treated patients, with a durability of response of 78% at 12 months and 62% at 18 months [4][10] - In a subset of 55 patients treated with one prior ROS1 TKI, the ORR was 51% with a durability of response of 93% at both the 12- and 18-month landmarks [4][12] Group 2: Efficacy and Safety - Zidesamtinib showed intracranial responses and activity against tumors with a ROS1 G2032R resistance mutation, with a well-tolerated safety profile [4][17] - The most frequent treatment-emergent adverse events (TEAEs) included peripheral edema (36%), constipation (17%), and fatigue (16%) [18][20] - Dose reductions due to TEAEs occurred in 10% of patients, and only 2% discontinued treatment due to TEAEs [20] Group 3: Future Development - The company is advancing clinical startup activities for the ALKAZAR Phase 3 trial, which will evaluate neladalkib, a novel ALK-selective inhibitor, against alectinib in TKI-naïve ALK-positive NSCLC patients [5][27] - Zidesamtinib has received breakthrough therapy designation for ROS1-positive metastatic NSCLC and orphan drug designation for ROS1-positive NSCLC [25][28] - The ongoing ARROS-1 trial is designed to evaluate zidesamtinib in both TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC [26][30]