Epidermal growth factor receptor (EGFR)-targeted photoimmunotherapy using cetuximab sarotalocan sodium (RM-1929) represents a novel therapeutic modality that induces selective tumor cell death and may influence the tumor immune microenvironment (TIME) in head and neck squamous cell carcinoma (HNSCC). Distinct TIME characteristics and potential immune remodeling, involving CD39+CD8+ T cell, were observed. These observations provide a rationale for further investigation of photoimmunotherapy as a strategy to integrate local tumor ablation with systemic immune modulation in recurrent HNSCC.

P3, N=412, Recruiting, Rakuten Medical, Inc.

P2/3, N=30, Not yet recruiting, Rakuten Medical Inc.

Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy.

ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

He received two cycles of intravenous methylprednisolone (1 g/day, 3 days/cycle) followed by oral prednisolone at 1 mg/kg/day, which was gradually tapered. Because cetuximab is a component of CS, CS-PIT has the potential to induce DIILD. Risk assessments and monitoring for DIILD are recommended for patients receiving CS-PIT.

In NIR-PIT, administration of cetuximab sarotalocan sodium is followed by laser irradiation of the affected area, which theoretically should induce tumor cell death. EGFR expression was positive in all cases and expression score showed no significant change between before and after treatment. These findings suggest that puncture interval plays a critical role in therapeutic outcomes, whereas EGFR expression may not directly influence treatment efficacy.

We observed and measured the drug accumulation and responses during treatment in humans using real-time fluorescence imaging. This information is expected to be applied to evaluate efficacy of NIR-PIT.

P2, N=27, Not yet recruiting, Roswell Park Cancer Institute | Initiation date: May 2025 --> Sep 2025

This study demonstrated that combining endoscopic photoimmunotherapy with nivolumab is safe and feasible for advanced gastric cancer.

P2, N=27, Not yet recruiting, Roswell Park Cancer Institute

P1/2, N=23, Active, not recruiting, Rakuten Medical, Inc. | N=74 --> 23 | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2026