Aligned with FDA on NDA submission strategy for TKI pre-treated patients with advanced ROS1-positive NSCLC and participation in Real-Time Oncology Review; the company plans to initiate a rolling NDA submission in July 2025 with target completion in the third quarter of 2025
In 117 ROS1 TKI pre-treated patients, including 50% who had received ≥ 2 prior ROS1 TKIs ± chemotherapy, ORR by BICR was 44% (95% CI: 34, 53) 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 (crizotinib or entrectinib) ± chemotherapy, ORR was 51% (95% CI: 37, 65) with initial estimated durability of response of 93% at the 12- and 18-month landmarks
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
Company announces progress in the front-line development strategies for its parallel lead programs in ROS1-positive and ALK-positive NSCLC
Company to host a conference call today, June 24th at 8:00am ET
CAMBRIDGE, Mass., June 24, 2025 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced positive pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI (tyrosine kinase inhibitor) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from the global ARROS-1 Phase 1/2 clinical trial.
In addition, Nuvalent announced progress on the front-line development strategies for its parallel lead programs in ROS1-positive and ALK-positive NSCLC, including:
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The first report of preliminary data from the Phase 2 TKI-naïve cohort in its ARROS-1 clinical trial, in which global enrollment is ongoing; and,
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The advancement of clinical startup activities to support the global initiation of the ALKAZAR Phase 3, randomized, controlled trial. The trial is designed to evaluate neladalkib, a novel ALK-selective inhibitor, versus alectinib, a front-line standard of care, for the treatment of patients with TKI-naïve ALK-positive NSCLC, and the company expects to begin enrollment early in the second half of 2025.
The company completed a pre-New Drug Application (NDA) meeting with the U.S. Food and Drug Administration (FDA) and aligned on its plans to move forward with an NDA submission seeking an indication for the treatment of zidesamtinib for TKI pre-treated patients with locally advanced or metastatic ROS1-positive NSCLC. The FDA agreed to accept the NDA for participation in the Real-Time Oncology Review (RTOR) pilot program, which facilitates earlier submission of topline data to support an earlier start to the FDA's evaluation of the application. The company plans to initiate a rolling NDA submission in July 2025 with completion targeted for the third quarter of 2025, and continues to engage with the FDA on potential opportunities for line-agnostic expansion.
"Continued innovation for patients with ROS1-positive NSCLC is needed. Limitations of currently available ROS1 TKIs can lead to trade-offs between efficacy and tolerability in the front-line, and there is no clear targeted therapy care standard for TKI pre-treated patients," said Alexander Drilon, MD, ARROS-1 trial investigator and Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. "These data demonstrate the potential for zidesamtinib to deliver meaningful clinical outcomes for TKI pre-treated patients, including those progressing with brain metastases or treatment-emergent resistance mutations, and to offer a favorable tolerability profile consistent with its goal of avoiding off-target side effects through ROS1-selectivity."
"Bringing a drug from ideation to pivotal data in just a few short years is a rare opportunity, and I would like to express my sincere gratitude for the tireless dedication of the Nuvalent team and for the patients, caregivers, and investigators that have helped us achieve this milestone for zidesamtinib," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Today's announcement brings us a critical step closer to achieving our goal of becoming a fully integrated, commercial-stage biopharmaceutical company able to deliver a new, potential best-in-class treatment option to all patients with advanced ROS1-positive NSCLC."
"Ongoing research and efforts to develop more effective, targeted therapies for people living with ROS1-positive lung cancer align closely with our mission at The ROS1ders," said Janet Freeman-Daily, Co-Founder and President of The ROS1ders. "Today's announcement brings renewed hope to our community—for more options and the potential for more precious time with our loved ones."
About Neladalkib and the ALKAZAR Phase 3 Clinical Trial
Neladalkib is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is 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. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.
ALKAZAR is a Phase 3 global, randomized, controlled trial designed to enroll approximately 450 patients with TKI-naïve ALK-positive NSCLC. Patients will be randomized 1:1 to receive neladalkib monotherapy or ALECENSA® (alectinib) monotherapy. The primary endpoint is progression free survival (PFS) based on Blinded Independent Central Review (BICR). Secondary endpoints include PFS based on investigator's assessment, and BICR assessment of objective response rate (ORR), intracranial objective response rate (IC-ORR), overall survival (OS), and safety.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent 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.