Nuvalent, Inc. (Nasdaq: NUVL) is accelerating its path to potential FDA approval, targeting 2026 for zidesamtinib in TKI pre-treated ROS1-positive non-small cell lung cancer (NSCLC). The company's "OnTarget 2026" plan includes key milestones in 2025, including NDA submission for zidesamtinib and pivotal data readouts for both zidesamtinib and neladalkib. This strategy reflects Nuvalent's focus on delivering precisely targeted therapies for clinically validated kinase targets in cancer.
Anticipated 2025 Milestones
Nuvalent anticipates several key milestones in 2025:
- Zidesamtinib (ARROS-1 Trial): Reporting pivotal data from the ARROS-1 Phase 1/2 trial in TKI pre-treated patients with advanced ROS1-positive NSCLC in the first half of 2025.
- Zidesamtinib NDA Submission: Submitting a New Drug Application (NDA) for zidesamtinib with an initial target indication for TKI pre-treated patients with advanced ROS1-positive NSCLC by mid-2025.
- Neladalkib (NVL-655) (ALKOVE-1 Trial): Reporting pivotal data from the ALKOVE-1 Phase 1/2 trial in TKI pre-treated patients with advanced ALK-positive NSCLC by year-end 2025.
- Neladalkib (ALKAZAR Trial): Initiating the ALKAZAR Phase 3 randomized, controlled trial of neladalkib for TKI-naïve patients with ALK-positive NSCLC in the first half of 2025.
- NVL-330 (HEROEX-1 Trial): Progressing the HEROEX-1 Phase 1a/1b trial of NVL-330 for patients with advanced HER2-altered NSCLC.
Clinical Trial Enrollment Updates
As of December 31, 2024:
- ARROS-1 (ROS1-positive NSCLC): A total of 430 Phase 1 and Phase 2 patients have been enrolled in the ongoing ARROS-1 Phase 1/2 trial of zidesamtinib. The trial is designed with registrational intent for both TKI pre-treated and TKI-naïve patients with advanced ROS1-positive NSCLC. Updated Phase 1 data were presented at the ESMO Congress in September 2024.
- ALKOVE-1 (ALK-positive NSCLC): A total of 596 Phase 1 and Phase 2 patients have been enrolled in the ongoing ALKOVE-1 Phase 1/2 trial of neladalkib. The trial is designed with registrational intent for TKI pre-treated patients. Updated Phase 1 data were presented at the ESMO Congress in September 2024.
Nuvalent's Pipeline and Strategy
Nuvalent is focused on developing therapies that overcome the limitations of existing kinase inhibitors. Zidesamtinib is a brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance, including those with the G2032R mutation. It also aims to improve treatment options for patients with brain metastases and avoid TRK-related CNS adverse events.
Neladalkib is a brain-penetrant ALK-selective inhibitor designed to remain active in tumors resistant to first-, second-, and third-generation ALK inhibitors, including those with the G1202R mutation. Similarly, it is designed for CNS penetration and to avoid TRK inhibition.
NVL-330 is a HER2-selective tyrosine kinase inhibitor designed to treat HER2-mutant tumors, including those with exon 20 insertion mutations, while avoiding EGFR inhibition and treating brain metastases.
Management Commentary
"2025 marks our opportunity to transition to becoming a fully integrated commercial-stage biopharmaceutical company," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Enrollment momentum in the Phase 2 portions of our ARROS-1 and ALKOVE-1 clinical trials has further accelerated following our presentation of updated Phase 1 data at ESMO 2024, reinforcing our plan to report pivotal data from both programs this year."
Darlene Noci, A.L.M., Chief Development Officer at Nuvalent, added, "Parallel development paths are in place towards our ultimate goal to provide new, potential best-in-class treatment options to all patients with ROS1- or ALK-positive NSCLC. For zidesamtinib, we plan to submit an NDA this year with an initial target indication for TKI pre-treated patients with ROS1-positive NSCLC."
Alexandra Balcom, Chief Financial Officer at Nuvalent, stated, "We believe we have the right team in place and are well resourced with cash runway into 2028 to support the advancement of our clinical programs and ongoing buildout of a commercial infrastructure."
