Nuvalent has submitted a New Drug Application (NDA) to the FDA for neladalkib (NVL-655), an ALK-targeted therapy for advanced ALK-positive non–small cell lung cancer (NSCLC) in patients previously treated with tyrosine kinase inhibitors (TKIs). The submission is based on the Phase 1/2 ALKOVE-1 trial, which included patients treated with lorlatinib or chemotherapy.
The trial showed strong results, especially in lorlatinib-naive patients, with a 46% response rate and 60% maintaining response at 18 months. Patients with the G1202R mutation responded even better. Neladalkib also demonstrated effective brain activity, with a 63% response rate in patients with measurable brain metastases.
The drug was generally well tolerated. Common side effects included liver enzyme increases, constipation, taste changes, and nausea. Only 5% discontinued treatment, while 17% required dose reductions. The FDA granted Breakthrough Therapy Designation in May 2024, and the NDA was submitted within four years of the first clinical trial. Full trial data will be presented at an upcoming medical meeting.