Neladalkib Earns FDA Priority Review in ALK-Positive NSCLC

The FDA has granted priority review to neladalkib as a treatment for those with advanced ALK-positive non–small cell lung cancer (NSCLC) who have received prior therapy with tyrosine kinase inhibitors (TKIs), according to a press release from the developer, Nuvalent, Inc.¹

The agency assigned a Prescription Drug User Fee Act date of November 27, 2026, for approving neladalkib in this NSCLC population. Developers previously submitted the new drug application for neladalkib in April 2026.²

Supporting data for the application came from the phase 1/2 ALKOVE-1 trial (NCT05384626) assessing neladalkib among patients with ALK-positive NSCLC and other solid tumors. Previous data showed that after a data cutoff of September 30, 2024, among 253 patients who received prior TKIs, the overall response rate (ORR) was 31% (95% CI, 26%-37%).³ Responses were sustained for at least 6 months, 12 months, and 18 months in 76% (95% CI, 64%-84%), 64% (95% CI, 51%-75%), and 53% (95% CI, 34%-68%) of those with a response, respectively.

Among 63 patients who received prior TKIs but had no previous treatment with lorlatinib (Lorbrena), data showed an ORR of 46% (95% CI, 33%-59%). Additionally, responses were sustained for at least 6 months, 12 months, and 18 months in 89% (95% CI, 69%-96%), 80% (95% CI, 58%-91%), and 60% (95% CI, 19%-85%) of responders in this group, respectively.

In a cohort of 92 patients with prior TKIs and measurable central nervous system (CNS) lesions, the intracranial ORR was 32% (95% CI, 22%-42%), with an intracranial duration of response (DOR) rate of 81% (95% CI, 59%-91%), 71% (95% CI, 48%-85%), and 71% (95% CI, 48%-85%) for at least 6 months, 12 months, and 18 months, respectively. Among those with prior TKIs and no previous treatment with lorlatinib who had measurable CNS lesions (n = 24), the intracranial ORR was 63% (95% CI, 41%-81%), with 92% (95% CI, 57%-99%) of responders maintaining their intracranial responses for at least 18 months.

Among 656 patients with ALK-positive NSCLC who received neladalkib at the recommended phase 2 dose (RP2D), the most common treatment-emergent adverse effects (TEAEs) of any grade included increased alanine aminotransferase (47%), increased aspartate aminotransferase (44%), constipation (28%), dysgeusia (23%), peripheral edema (18%), cough (16%), and nausea (16%). Additionally, 17% of patients required dose reductions and 5% discontinued study therapy due to TEAEs.

Investigators will present additional findings from the TKI-pretreated cohort of the ALKOVE-1 trial, as well as the TKI-naïve group, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.Previously, developers announced that the FDA accepted a new drug application for zidesamtinib as a treatment for patients with advanced or metastatic ROS1-positive NSCLC in November 2025.⁴

“With today's announcement, new drug applications for both zidesamtinib and neladalkib in TKI-pretreated populations are now under review with the FDA, and TKI-naïve expansion strategies are underway,” James Porter, PhD, chief executive officer at Nuvalent, stated in the press release.¹ “Our US commercial and medical affairs teams are in place and focused on establishing the strong foundational systems and infrastructure required to effectively deliver on multiple synergistic launches in biomarker-driven NSCLC.”

The phase 1 portion of the first-in-human ALKOVE-1 trial was designed to evaluate the overall safety and tolerability of neladalkib among patients with ALK-positive NSCLC who received at least 1 ALK-TKI or patients with other previously treated ALK-positive solid tumors. Other objectives in the phase 1 portion included determining the RP2D, pharmacokinetics, and preliminary anti-tumor activity.

Enrollment for the phase 2 portion of the ALKOVE-1trial remains ongoing among adult and adolescent patients with ALK-positive solid tumors and adolescents with ALK-positive NSCLC.

References

1. Nuvalent announces key program and business updates, strengthening foundation for global leadership in ROS1- and ALK-positive NSCLC. News release. Nuvalent, Inc. May 27, 2026. Accessed May 28, 2026. https://tinyurl.com/4843y6yp
2. 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 May 28, 2026. https://tinyurl.com/5e2wyd3e
3. 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 May 28, 2026. https://tinyurl.com/mtu8vjw5
4. Nuvalent announces FDA acceptance of new drug application for zidesamtinib for the treatment of TKI pre-treated patients with advanced ROS1-positive NSCLC. News release. Nuvalent, Inc. November 19, 2025. Accessed May 28, 2026. https://tinyurl.com/2wukrj6d