Nuvalent submits FDA NDA for neladalkib, a brain-penetrant ALK-selective inhibitor, in TKI-pretreated advanced ALK-positive NSCLC based on ALKOVE-1 Phase 1/2 trial data
Written By: Anand Sathappan, BPharm
Reviewed By: Pharmacally Editorial Team
Nuvalent, Inc. announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for neladalkib, an investigational ALK-selective inhibitor, for patients with tyrosine kinase inhibitor (TKI) pre-treated advanced ALK-positive non-small cell lung cancer (NSCLC). The submission is supported by data from the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial (NCT05384626).
The company noted that neladalkib advanced from first clinical trial initiation to NDA submission in less than four years. Chief Development Officer Darlene Noci stated that the timeline reflects the company’s focus on the ALK-positive NSCLC community, adding that Nuvalent plans to work closely with the FDA during the review process.
ALKOVE-1 Trial Data Supporting NDA
The application is based on results in TKI-pretreated patients with advanced ALK-positive NSCLC enrolled in the ALKOVE-1 Phase 1/2 study. Neladalkib demonstrated antitumor activity, including intracranial responses. The therapy also addressed key drivers of disease progression and showed a generally well-tolerated safety profile consistent with its ALK-selective, TRK-sparing design. Detailed results are planned for presentation at a future medical meeting.
Neladalkib previously received breakthrough therapy designation for patients with locally advanced or metastatic ALK-positive NSCLC treated with two or more prior ALK TKIs. The therapy has also received orphan drug designation for ALK-positive NSCLC.
Neladalkib Mechanism and Design
Neladalkib is a brain-penetrant, ALK-selective inhibitor designed to overcome resistance associated with currently available ALK inhibitors. The agent is intended to remain active in tumors that develop resistance to first-, second-, and third-generation ALK inhibitors, including those with single or compound treatment-emergent ALK mutations such as G1202R.
The therapy is also designed for central nervous system penetration to address brain metastases while avoiding inhibition of tropomyosin receptor kinase (TRK). This TRK-sparing approach aims to reduce TRK-related central nervous system adverse events associated with dual TRK/ALK inhibitors.
ALKOVE-1 Phase 1/2 Trial Design
The ALKOVE-1 trial is a first-in-human Phase 1/2 study evaluating neladalkib in patients with advanced ALK-positive NSCLC and other ALK-positive solid tumors. The completed Phase 1 portion enrolled patients previously treated with at least one ALK TKI or those with other ALK-positive tumors lacking satisfactory standard therapy. Objectives included safety and tolerability, pharmacokinetics, determination of the recommended Phase 2 dose, and preliminary antitumor activity.
The global, single-arm, open-label Phase 2 portion is designed with registrational intent in TKI-pretreated advanced ALK-positive NSCLC. Enrollment continues for adult and adolescent patients with ALK-positive solid tumors outside NSCLC, as well as adolescent patients with ALK-positive NSCLC.
Reference
Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC, 07 April 2026, https://investors.nuvalent.com/2026-04-07-Nuvalent-Announces-Submission-of-New-Drug-Application-to-FDA-for-Neladalkib-in-TKI-Pre-treated-Advanced-ALK-positive-NSCLC
A Study of Neladalkib (NVL-655) in Patients with Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1), ClinicalTrials.gov ID NCT05384626, https://clinicaltrials.gov/study/NCT05384626
About the Writer
Anand Sathappan is a pharmacy graduate with interests in pharmaceutical sciences, pharmacology, and medical writing. He also holds certification in medical coding and has familiarity with pharmacology and healthcare documentation. His work focuses on exploring developments in pharmaceuticals and presenting scientific information in a clear and structured manner.