ALK‑Vac peptide vaccine (ALK resistance‑mutation neoantigens) elicits T‑cell responses with 93% disease control on ALK TKIs

ALK‑Vac is a prophylactic synthetic long‑peptide vaccine designed to immunize against seven common ALK kinase–domain resistance mutations (I1171T/N/S, L1196M, G1202R, D1203N, E1210K) and was given with poly‑ICLC while patients stayed on their standard ALK TKI in this first‑in‑human Phase 1b ARCHER trial (NCT05950139). In advanced ALK+ NSCLC without progression on TKI (n=15; 87% on first‑line TKI; concomitant alectinib 47%, lorlatinib 33%, brigatinib 20%; 67% with no measurable disease), the regimen was well tolerated (no Grade ≥3 TRAEs; mostly Grade 1 injection‑site reactions 93%, fatigue 60%, flu‑like symptoms 40%) and generated vaccine‑specific IFN‑γ ELISpot responses in 71% (10/14 evaluable; median 11.9‑fold increase). With median follow‑up 11.5 months, disease control rate was 93% (14/15); however, in this minimal‑residual‑disease‑enriched cohort the “efficacy” bar is unusually easy to clear—frontline ALK TKIs already deliver long PFS (e.g., alectinib median PFS 25.7 months in ALEX; lorlatinib median PFS not reached at 5 years in CROWN), so DCR at ~1 year is not yet evidence of delayed resistance.