Nuvalent has aligned with the U.S. FDA on its NDA submission strategy for the company’s oral tyrosine kinase inhibitor, zidesamtinib, in TKI pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC).
In the phase 1/2 ARROS-1 clinical trial, among 117 ROS1 heavily TKI pre-treated patients the overall response rate was 44% with initial estimated durability of response of 78% at the 12-month landmark and 62% at the 18-month landmark. In the subset of 55 patients treated with 1 prior ROS1 TKI, overall response rate was 51% with initial estimated durability of response of 93% at the 12- and 18-month landmarks.
According to Nuvalent, zidesamtinib demonstrated intracranial responses, activity against tumors with a ROS1 G2032R resistance mutation, and a generally well-tolerated safety profile, including low rates of dose reduction (10%) and discontinuation (2%), consistent with its ROS1-selective, TRK-sparing design.
Nuvalent plans to initiate a rolling NDA submission in July 2025 with target completion in the third quarter of 2025.
If approved, the drug will enter a space that is growing increasingly crowded. Bristol Myers Squibb’s TKI inhibitor, Augtyro, was approved in November 2023. Earlier this month, Nuvation Bio’s oral TKI inhibitor, Ibtrozi, was also approved for the treatment of locally advanced or metastatic ROS1-positive NSCLC.