Nuvalent Submits NDA for Neladalkib in ALK+ NSCLC After TKIs

Nuvalent has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for neladalkib for the treatment of 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 phase 1/2 ALKOVE-1 clinical trial, which evaluated neladalkib in patients with advanced ALK-positive NSCLC who had previously received ALK-targeted TKIs. In this population, the investigational agent demonstrated overall antitumor activity, including intracranial responses. The therapy was also reported to address key drivers of disease progression in this setting, where resistance to prior ALK inhibitors commonly emerges.

Although detailed efficacy data have not yet been disclosed, the company noted that neladalkib showed encouraging activity in patients whose disease had progressed following prior TKI treatment. The agent’s ability to generate intracranial responses is notable given the frequency of brain metastases in patients with ALK-positive NSCLC. These findings may have implications for oncology nurses monitoring neurologic symptoms and disease progression in clinical practice.

Neladalkib is a brain-penetrant, ALK-selective inhibitor designed to overcome limitations associated with currently available ALK-directed therapies. The drug is intended to remain active in tumors that develop resistance to first-, second-, and third-generation ALK inhibitors. This includes activity against treatment-emergent ALK mutations, such as single and compound mutations like G1202R, which are known to contribute to disease progression.

In addition to its activity against resistant disease, neladalkib has been designed to avoid inhibition of the tropomyosin receptor kinase (TRK) family. This TRK-sparing approach may reduce the risk of central nervous system adverse effects that have been observed with dual TRK/ALK inhibitors. For oncology nurses, this design feature may be relevant when assessing neurologic tolerability and managing treatment-related toxicities.

The safety profile of neladalkib in the ALKOVE-1 trial was described as generally well tolerated and consistent with its selective mechanism of action. While specific adverse event rates were not reported in the announcement, the tolerability profile may be an important consideration for nurses involved in patient education, toxicity monitoring, and supportive care.

The ALKOVE-1 trial (NCT05384626) is a first-in-human, open-label phase 1/2 study evaluating neladalkib in patients with advanced ALK-positive NSCLC and other solid tumors. The completed phase 1 portion enrolled patients with ALK-positive NSCLC who had received at least 1 prior ALK TKI, as well as patients with other ALK-positive solid tumors who were previously treated or lacked satisfactory standard-of-care options. This portion of the trial assessed safety, tolerability, pharmacokinetics, and preliminary antitumor activity, and established the recommended phase 2 dose.

The ongoing phase 2 portion of ALKOVE-1 is designed with registrational intent and is focused on patients with TKI pre-treated advanced ALK-positive NSCLC. The study is being conducted globally and continues to enroll additional patient populations, including those with ALK-positive solid tumors outside of NSCLC and adolescent patients with ALK-positive malignancies.

Neladalkib has received breakthrough therapy designation from the FDA for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have previously been treated with 2 or more ALK TKIs. The agent has also been granted orphan drug designation for ALK-positive NSCLC, reflecting the unmet need in this patient population.

Further data from the ALKOVE-1 trial are expected to be presented at a future medical meeting, which may provide additional insights into the efficacy and safety profile of neladalkib in this setting.

Reference

Nuvalent, Inc. Nuvalent announces submission of new drug application to FDA for neladalkib in TKI pre-treated advanced ALK-positive NSCLC. Published April 7, 2026. Accessed April 7, 2026.