ALKOVE-1
The registrational study of a fourth-generation ALK pill designed to work after lorlatinib and to spare the brain-related side effects.
In 253 TKI-pretreated patients, ORR by blinded review was 31% with intracranial responses and activity against compound resistance mutations (G1202R, G1202R/L1196M). NDA submitted April 2026 with priority review; PDUFA date 27 November 2026. ALKAZAR (vs alectinib, first line) recruiting.
Setting
ALK-positive NSCLC after prior ALK TKIs (including lorlatinib): neladalkib single arm
Phase
Phase 1/2
Sponsor
Nuvalent
Registry
Headline result
ORR 31% in heavily pretreated ALK+ NSCLC; NDA under priority review.
Reported
2025
Enrolled
432
Replication
Single-arm pivotal; ALKAZAR (randomised vs alectinib, first line) is ongoing.
In plain words
What these results mean for people, not percentages
Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort)primaryresponse endpoint
- 51 out of 100 people had their tumour shrink with Neladalkib, lorlatinib-pretreated.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- These results apply to the people the trial enrolled: ALK-positive NSCLC after prior ALK TKIs (including lorlatinib): neladalkib single arm. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (ALK); the result should not be assumed for people whose cancer does not have it.
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.
432 participants enrolled.
Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort)primary
Neladalkib, lorlatinib-pretreated51 of 100
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort)primary | Neladalkib, lorlatinib-pretreated | — | 51% | — | — | link |
Replication
Single-arm pivotal; ALKAZAR (randomised vs alectinib, first line) is ongoing.