Neladalkib (next-gen ALK TKI; TRK-sparing) posts 31% ORR post–multiple ALK TKIs, with 68% ORR in G1202R ALK+ NSCLC

Neladalkib is an investigational, brain-penetrant ALK tyrosine kinase inhibitor designed to cover single/compound ALK resistance mutations (including G1202R) while sparing TRK, evaluated in the global single-arm Phase 1/2 ALKOVE-1 trial (NCT05384626; data cut Aug 29, 2025). In the Phase 2 efficacy-evaluable, ALK TKI–pretreated cohort (n=253; median 3 prior therapies; 78% had ≥2 prior ALK TKIs and 91% had prior lorlatinib; 40% CNS disease), BICR ORR was 31% (79/253; 64% had DOR ≥12 months), with intracranial ORR 32% (29/92) and intracranial DOR ≥12 months 71%; activity enriched in G1202R (ORR 68% [32/47]) and in lorlatinib-naïve pretreated patients (ORR 46% [29/63], IC-ORR 63% [15/24]). While cross-trial comparisons are imperfect, post-TKI options often fall back to chemotherapy or docetaxel±ramucirumab with modest response rates (e.g., ORR 23% with docetaxel+ramucirumab in REVEL), so a 31% ORR with durable responses—plus a high G1202R ORR—suggests meaningful “targeted” salvage potential; however, the abstract does not yet detail Grade ≥3 AEs/discontinuations, limiting a real tolerability readout versus chemo.