Developers Submit NDA for Neladalkib in Pretreated ALK+ NSCLC

Developers from Nuvalent have submitted a new drug application (NDA) for neladalkib, an investigational ALK-selective inhibitor, as a therapy for patients with advanced ALK-positive non–small cell lung cancer (NSCLC) who have received prior tyrosine kinase inhibition (TKIs), according to a press release from the developers.¹

According to the press release, the FDA has previously granted breakthrough therapy designation to neladalkib as a treatment for those with ALK-positive NSCLC who have received at least 2 prior TKIs. Additionally, the agent previously earned orphan drug designation as a treatment for patients with ALK-positive NSCLC.

Supporting data for the NDA came from the phase 1/2 ALKOVE-1 trial (NCT05384626) assessing neladalkib among those with ALK-positive NSCLC and other solid tumors. According to topline findings shared regarding all patients with solid tumors in November 2025, the objective response rate (ORR) was 31% (n = 79/253; 95% CI, 26%-37%) among patients who received any prior ALK-TKI with or without chemotherapy and 46% (n = 29/63; 95% CI, 33%-59%) among those who received prior TKIs but had no prior lorlatinib (Lorbrena).² The duration of response (DOR) rates in each respective population were 76% (95% CI, 64%-84%) and 89% (95% CI, 69%-96%) for at least 6 months, 64% (95% CI, 51%-75%) and 80% (95% CI, 58%-91%) for at least 12 months, and 53% (95% CI, 34%-68%) and 60% (95% CI, 19%-85%) for at least 18 months.

Among 44 patients with ALK-positive NSCLC and no prior TKIs, the preliminary ORR was 86% (n = 38/44), which included complete responses (CRs) in 9% (n = 4/44). The DOR ranged from 1.7+ to 14.8+ months in this population. Among 9 patients with evaluable intracranial lesions, the intracranial ORR was 78% (n = 7/9), with an intracranial CR rate of 44% (n = 4/9).

Findings from the ALKOVE-1 trial demonstrated a well-tolerated safety profile for neladalkib. Among 656 patients with advanced ALK-positive NSCLC, the most common treatment-emergent adverse effects (TEAEs) included increased alanine aminotransferase (47%), increased aspartate aminotransferase (44%), constipation (28%), dysgeusia (23%), peripheral edema (18%), cough (16%), and nausea (16%).

Developers intend to share detailed findings from the ALKOVE-1 trial at a later medical conference.

“The advancement of neladalkib from first clinical trial initiation to NDA submission in less than 4 years represents a remarkable pace in oncology drug development, underscoring the vigor and urgency our team brought to this program and our deep commitment to the ALK-positive NSCLC community,” Darlene Noci, ALM, chief development officer at Nuvalent, stated in the press release.¹ “We would like to extend our sincere gratitude to the patients, families and investigators who have made this progress possible, and are committed to working closely with the FDA throughout the NDA review process toward our goal of bringing neladalkib to patients as quickly as possible.”

The completed phase 1 portion of the ALKOVE-1 trial included patients with ALK-positive NSCLC who received at least 1 ALK TKI or those with other ALK-positive solid tumors. This component of the trial evaluated the overall safety and tolerability of neladalkib; additional end points included the recommended phase 2 dose, pharmacokinetics, and preliminary anti-tumor activity.

The international phase 2 portion of the trial was designed with registrational intent for patients with ALK-positive NSCLC who received prior TKIs. Enrollment across the world is underway for adults and adolescents with ALK-positive tumors apart from NSCLC as well as adolescent patients with ALK-positive NSCLC.

References

1. Nuvalent announces submission of new drug application to FDA for neladalkib in TKI pre-treated advanced ALK-positive NSCLC. News release. Nuvalent, Inc. April 7, 2026. Accessed April 7, 2026. https://tinyurl.com/5e2wyd3e
2. Nuvalent announces positive topline pivotal data from ALKOVE-1 clinical trial of neladalkib for TKI pre-treated patients with advanced ALK-positive NSCLC. News release. Nuvalent, Inc. November 17, 2025. Accessed April 7, 2026. https://tinyurl.com/mtu8vjw5