A phase 3, randomized, double-arm, open-label, controlled study of ASP-1929 photoimmunotherapy (PIT) versus physician’s choice standard of care (SOC) for patients with locoregional, recurrent head and neck squamous cell carcinoma (HNSCC).

6080 Background: Locoregional recurrence is the main cause of morbidity and mortality in HNSCC, yet therapeutic choices are limited by sequelae of previous treatment and the potential for significant loss of function. ASP-1929 PIT is a novel cancer-targeted technology, utilizing an anti-EGFR monoclonal antibody conjugated to the dye IR700, that is activated by 690 nm light to induce rapid selective tumor cell destruction and trigger immune response. Methods: This global phase 3 study was conducted at 40 study centers located in the US, Taiwan, Japan, India, and Ukraine. Patients with locoregionally recurrent HNSCC who had failed or progressed on or after at least 2 lines of therapy were randomized 2:1 to the PIT arm or SOC. The planned sample size was 275. In the PIT arm, each cycle consisted of ASP-1929 infusion (640 mg/m 2 ) on Day 1, followed 24 ± 4 hours later by illumination (50 J/cm 2 superficial and/or 100 J/cm interstitial). Retreatment occurred ≥4 weeks apart, based on tumor response, for up to 8 cycles. In the control arm, patients received the physician’s choice of standard of care (docetaxel, cetuximab, methotrexate, or paclitaxel) until disease progression, intolerable adverse effects, or discontinuation of study treatment. Safety and efficacy outcomes were evaluated, with a data cutoff of 30 April 2025. Results: Active patient enrollment was discontinued due to challenges in patient recruitment and changes in the SOC landscape. As of 17 December 2024, 135 patients had been enrolled, with 68 patients experiencing progression or death and 36 patients in the ongoing long-term survival follow-up phase of the study. Median age was 62.0 years; 80.7% were male. In PIT and SOC arms, 64.0% and 63.0% of patients had received ≥ 3 prior therapy lines. Despite similar progression-free survival (HR 0.91; 95% CI 0.24 - 3.45), median overall survival was 15.7 months in the PIT arm compared to 9.6 months in the SOC arm (HR 0.83; 95% CI 0.50 - 1.36). Objective response rate was 25.8% in the PIT arm and 15.2% in the SOC arm, and disease control rate was 68.5% and 43.5%, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58.3% of patients in the PIT arm and 36.4% of patients in SOC; however, fewer TEAEs led to dose modification, delay, or interruption in the PIT arm (15.5% vs 30.3%). Conclusions: Considering the limitations of the study data, these results support ASP-1929 PIT as a tolerable and clinically active treatment option for locoregional, recurrent HNSCC and its ongoing evaluation in the current randomized global Phase 3 ASP-1929-381 study. Clinical trial information: NCT03769506 .