ASP-1929 (EGFR–IR700 photoimmunotherapy) lifts OS to 15.7mo vs 9.6mo in heavily pretreated recurrent HNSCC, but underpowered

ASP-1929 photoimmunotherapy (PIT) is an anti‑EGFR monoclonal antibody–IR700 dye conjugate activated by 690nm light to cause localized tumor cell kill (and potentially immune priming); it was tested in a global Phase 3, randomized (2:1), open-label trial in locoregionally recurrent HNSCC after ≥2 prior lines (planned n=275; enrolled n=135; data cutoff April 30, 2025; NCT03769506). Efficacy numerically favored PIT with median OS 15.7 vs 9.6 months (HR 0.83; 95% CI 0.50–1.36) and ORR 25.8% vs 15.2% (DCR 68.5% vs 43.5%), while PFS was similar (HR 0.91; 95% CI 0.24–3.45); however, enrollment stopped early for recruitment/SOC shifts, so estimates are imprecise and cross-trial comparisons to current ICI-era sequences are shaky. Grade ≥3 TEAEs were higher with PIT (58.3% vs 36.4%), though fewer TEAEs drove dose modification/delay/interruption (15.5% vs 30.3%); as a benchmark, “physician’s choice” chemo arms in the pre-ICI era typically delivered ~6.9–8.4 month median OS in platinum-refractory R/M HNSCC trials, highlighting that the control OS here (9.6 months) is not unusually low for a late-line population but may not reflect today’s post–PD-1 treatment mix.