Background

To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye^®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC).

Methods

Patients received a single fixed dose (640 mg/m²) of RM-1929 and a fixed light treatment dose (50 J/cm² for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated.

Results

Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental 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 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.

中文翻译：

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RM-1929 光免疫疗法在日本复发性头颈部鳞状细胞癌患者中的 I 期、单中心、开放标签研究

背景

^{确定单周期RM} -1929 光免疫疗法的安全性、初步疗效、药代动力学和免疫原性细胞癌（rHNSCC）。

方法

患者接受单一固定剂量（640 mg/m ²）的 RM-1929 和固定光治疗剂量（50 J/cm ²用于表面照明；100 J/cm 光纤漫射器长度用于间质照明）。评估了安全性、肿瘤反应（通过中央放射学审查修改的 RECIST v1.1）、药代动力学和免疫原性。

结果

纳入了 3 名日本患者，他们之前接受过 ≥ 3 种治疗（包括放疗、化疗、西妥昔单抗和免疫治疗）均失败。靶病变为：颏下病变；右侧颈浅淋巴结病变和口咽部病变；和外耳道病变。所有患者都经历了≥1次治疗出现的不良事件（TEAE），但没有人被认为是剂量限制性的。TEAE 的严重程度为轻度至中度，除了一处 3 级应用部位疼痛是短暂的，在 24 小时内消退且无后遗症，并且不影响研究治疗的给药。报告的 17 例 TEAE 中有 13 例可能或可能与研究治疗有关。三名患者报告的应用部位疼痛和局部水肿被认为可能与研究治疗有关。在两名患者中观察到客观反应（均为部分反应）。第三名患者出现疾病进展。所有患者的 RM-1929 浓度和药代动力学参数相似。没有患者的抗药物抗体检测呈阳性。

结论

RM-1929 光免疫疗法在 rHNSCC 中显示出可控的安全性。这些经过大量预处理的患者的肿瘤反应具有临床意义，值得进一步研究。

临床试验注册

该试验在日本临床试验注册处注册为 jRCT2031200133。