背景:为了确定安全性,初步疗效,药代动力学,和单周期RM-1929光免疫疗法的免疫原性,与光活化染料(IRDye®700DX)缀合的抗EGFR抗体西妥昔单抗,在日本复发性头颈部鳞状细胞癌(rHNSCC)患者中。
方法:患者接受单一固定剂量(640mg/m2)的RM-1929和固定光治疗剂量(对于表面照明为50J/cm2;对于间质照明为100J/cm的纤维扩散器长度)。安全,肿瘤反应(通过中央放射学审查修改的RECISTv1.1),药代动力学,和免疫原性进行了评估。
结果:招募了3名日本患者,这些患者在包括放疗在内的3项先前治疗中失败,化疗,西妥昔单抗,和免疫疗法。目标病变为:颌下病变;右侧浅颈淋巴结病变和口咽病变;和外耳道病变。所有患者经历≥1次治疗紧急不良事件(TEAE),但没有一个被认为是剂量限制性的。TEAE的严重程度为轻度至中度,除了一个3级应用部位疼痛,这是短暂的,24小时内无后遗症,并且不影响研究治疗管理。报告的17种TEAE中有13种可能或可能与研究治疗有关。应用部位疼痛和局部水肿的三例患者报告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)。第三个病人有疾病进展。所有患者的RM-1929浓度和药代动力学参数相似。无患者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。
背景:该试验在日本临床试验注册中心注册为jRCT2031200133。
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.
BACKGROUND: The
trial was registered with the Japanese registry of clinical trials as jRCT2031200133.