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DLT assessments were conducted from Day 1 to Day 7

DLT assessments were conducted from Day 1 to Day 7. lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced??1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24?h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably Mouse monoclonal to HIF1A related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies. Conclusions RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation. Clinical trial registration The trial was registered with the Japanese registry of clinical trials as jRCT2031200133. Supplementary Information The online version Timegadine contains supplementary material available at 10.1007/s10147-021-01960-6. Keywords: RM-1929 (cetuximab sarotalocan), Photoimmunotherapy, Recurrent head and neck squamous cell carcinoma, Tumor-targeted monoclonal antibodies, Light-activatable dye (IRDye?700DX), Cetuximab-IR700DX conjugate Introduction Head and neck cancers, including cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, are the seventh most common cancer worldwide, accounting for nearly 900, 000 new cancer cases each year [1, 2]. In Asia, the number of new cases is estimated at?>?550,000 annually, more than half the worldwide total [2], and each year an estimated 300,000 deaths are attributed to the disease in Asia (5.6% of total cancer deaths) [3]. In Japan, the annual incidence and mortality of cancers of the oral cavity, pharynx, and larynx were projected at 27,700 and 8,900, respectively [4]. Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck cancers [5]. Approximately, 70% of patients with primary HNSCC present with locally or regionally advanced disease (stage III or IV) [6], which recurs in approximately 40C65% Timegadine of cases after primary therapy with surgery and radiation, with or without chemotherapy [6C10]. Patients with locally advanced HNSCC have a very poor prognosis, with a 5?year survival rate of only 10C50%, depending on the stage and location of the lesion [6]. Furthermore, patients with advanced disease have poor health-related quality of life (HRQoL) due to the physical effects of tumors affecting vital functions relating to speech and swallowing, and esthetic effects that can have profound emotional and social impacts [11]. Patients with progressive or recurrent HNSCC (rHNSCC) have limited treatment options [12, 13]. Combination chemotherapy regimens, including targeted therapies, yield objective response rates of 10C36% [14C16]. Although checkpoint inhibitors, such as nivolumab and pembrolizumab, have shown activity in rHNSCC, response rates and overall survival (OS) remain limited [17C21]. Treatment of locoregional disease in patients with advanced HNSCC improves disease-free survival and generally ensures long-term control [22C24]. However, there remains an unmet need for new treatment options to provide improved tumor response and locoregional control in patients with locoregional recurrent disease. Photoimmunotherapy utilizes tumor-targeted monoclonal antibodies conjugated with a light-activatable dye (IRDye?700DX, abbreviated as IR700) [25]. Preclinical data indicate that activation of the dye with non-thermal red light results in rapid anticancer activity, which is mediated by biophysical processes that disrupt the membrane integrity of tumor cells (Fig.?1A) [26, 27]. In preclinical studies, photoimmunotherapy induced tumor Timegadine necrosis and immunogenic cell death that can lead to activation of innate and adaptive immunity [28]. Open in a separate window Fig. 1 Photoimmunotherapy mechanism of action and RM-1929 photoimmunotherapy overview. A Tumor-targeted antibody is conjugated.