Biopharmaceutical company Nuvalent Inc (Nasdaq: NUVL) announced on Monday that it has dosed the first patient in its global Phase 3 ALKAZAR trial, evaluating neladalkib as a first-line treatment for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have not previously received tyrosine kinase inhibitors (TKIs). The randomised, controlled trial will compare neladalkib monotherapy against alectinib (ALECENSA), a current standard of care.

Approximately 450 patients will be enrolled, with the primary endpoint being progression-free survival (PFS) assessed by blinded independent central review. Secondary endpoints include overall survival, intracranial response measures, objective response rate and safety. The trial design aligns with feedback from global regulatory agencies.

Neladalkib is also under evaluation in the Phase 2 ALKOVE-1 trial for TKI-pretreated ALK-positive NSCLC. Early data has shown durable clinical responses in heavily pre-treated patients, including those with brain metastases and compound resistance mutations, while maintaining a favorable safety profile.

Designed as a brain-penetrant, ALK-selective, TRK-sparing inhibitor, neladalkib targets resistance mutations and aims to minimize CNS-related adverse events seen with dual ALK/TRK inhibitors. It holds Breakthrough Therapy and Orphan Drug designations for ALK-positive NSCLC. Topline data from the ALKOVE-1 Phase 2 trial is expected by year-end 2025.