Feasibility study of photoimmunotherapy combination with ASP-1929 for vulvar, vaginal, and cervical cancer

Objective:The aim of this study was to evaluate the feasibility of photoimmunotherapy (PIT) using ASP-1929, an anti-epidermal growth factor receptor (EGFR) antibody-dye conjugate, for vulvar, vaginal, and cervical cancers by validating EGFR expression and establishing immunohistochemistry (IHC)-based eligibility criteria for a phase II trial, HICARi study.Methods: Cetuximab-binding activity was analyzed in gynecologic cancer cell lines (CaSki, HeLa, and Ishikawa) using flow cytometry and compared with positive controls (A431 and BxPC-3) and a low-EGFR control (MCF-7).IHC was performed on cell blocks and clinical specimens of vulvar, vaginal, and cervical cancers (validation cohort, n=27; screening cohort, n=40).Results: CaSki demonstrated comparable or higher EGFR binding than BxPC-3, whereas HeLa and Ishikawa showed weaker binding.IHC staining intensity correlated with flow cytometry findings.Squamous cell carcinomas consistently exhibited moderate-to-strong EGFR expression, whereas non-squamous carcinomas displayed variable expression.EGFR positivity was defined as >30% of tumor cells with at least moderate membranous staining (2+ or 3+).In the validation cohort, EGFR positivity was observed in 71.4% of the vulvar, 80.0% of the vaginal, and 87.5% of the cervical cancers.The screening cohort showed similar rates: 88.9% of vulvar, 100% of vaginal, and 75.0% of cervical cancers. Conclusion:We demonstrated correlation between cetuximab-binding and IHC staining intensity, establishing IHC criteria (≥2+) for patient selection.EGFR positivity (71.4%-87.5%)indicates substantial eligibility for ASP-1929 PIT.Therapeutic efficacy will be evaluated in the HICARi study.