# ALKOVE-1

Source: https://onco.cc/trials/alkove-1/  
OnCo record `alkove-1` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The registrational study of a fourth-generation ALK pill designed to work after lorlatinib and to spare the brain-related side effects.

## Summary

ALKOVE-1, trial NCT05384626 sponsored by Nuvalent and reported in 2025, is the registrational phase 1/2 study of neladalkib, a fourth-generation ALK inhibitor designed to work after lorlatinib and to spare the brain-related side effects of earlier drugs. In 253 patients previously treated with ALK inhibitors, the objective response rate by blinded review was 31 percent, with intracranial responses and activity against compound resistance mutations such as G1202R, and the lorlatinib-pretreated pivotal cohort responded more often; a new drug application was submitted in April 2026 with priority review and a PDUFA date of 27 November 2026. OnCo links it to ALK as a target and to neladalkib, and the randomised ALKAZAR trial against alectinib in the first line is recruiting. As a single-arm study it cannot show superiority over existing options, which ALKAZAR will address.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT05384626
- Phase: 1/2
- Setting: ALK-positive NSCLC after prior ALK TKIs (including lorlatinib): neladalkib single arm
- Sponsor: Nuvalent
- Enrolled: 840
- Result: ORR 31% in heavily pretreated ALK+ NSCLC; NDA under priority review.
- Outcomes: Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort): Neladalkib, lorlatinib-pretreated 51%
- Replication: Single-arm pivotal; ALKAZAR (randomised vs alectinib, first line) is ongoing.

## Sources

- ClinicalTrials.gov NCT05384626: https://clinicaltrials.gov/study/NCT05384626
- Nuvalent NDA submission: https://investors.nuvalent.com/2026-04-07-Nuvalent-Announces-Submission-of-New-Drug-Application-to-FDA-for-Neladalkib-in-TKI-Pre-treated-Advanced-ALK-positive-NSCLC

## Connected records

- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/)
- drugs: [Neladalkib](https://onco.cc/drugs/neladalkib/)
- companies: [Nuvalent](https://onco.cc/companies/nuvalent/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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