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The registrational study of a fourth-generation ALK pill designed to work after lorlatinib and to spare the brain-related side effects.
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.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
840 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort)primary | Neladalkib, lorlatinib-pretreated | - | 51% | - | - | link |
Shares Neladalkib, Nuvalent, ALK-positive non-small-cell lung cancer, Small-molecule kinase inhibitors.
Shares ALK-positive non-small-cell lung cancer, ALK, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Small-molecule kinase inhibitors.
Shares Nuvalent, Small-molecule kinase inhibitors, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Small-molecule kinase inhibitors, Non-small-cell lung cancer.
Shares Nuvalent, Small-molecule kinase inhibitors.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Small-molecule kinase inhibitors, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.