Carrillo Jose, Gill Jaya Mini, Redfern Charles, Babic Ivan, Nomura Natsuko, Shah Dhaval K, Carrick Sean, Kesari Santosh
Hoag Family Cancer Institute, Hoag Memorial Hospital, Newport Beach, California, USA.
Department of Translational Neurosciences, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
Neurooncol Adv. 2024 Sep 30;6(1):vdae166. doi: 10.1093/noajnl/vdae166. eCollection 2024 Jan-Dec.
This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.
Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.
Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).
Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.
这项1期（NCT04396717）开放标签、多中心研究评估了IgG1单克隆抗体普利妥单抗在胶质瘤和脑转移瘤患者中的疗效。主要目的是评估普利妥单抗的安全性和/或耐受性，并确定其推荐的2期剂量（RP2D）。
复发性胶质瘤或脑转移瘤的成年患者入组当时开放的剂量队列。研究治疗包括在28天周期的第1、8、15和22天每周静脉注射一次普利妥单抗。评估安全性、药代动力学（PK）、药效学（PD）和临床活性。
15名患者在复发情况下接受了普利妥单抗治疗。普利妥单抗耐受性良好，未报告与普利妥单抗相关的严重不良事件。最常见的药物相关毒性是便秘和疲劳。未观察到剂量限制毒性，也未达到最大耐受剂量。因此，确定普利妥单抗的最大可行剂量和推荐的2期剂量为每周16.2mg/kg。在评估疗效的11名患者中，根据神经肿瘤学标准的反应评估，1名患者（9.1%）表现出部分缓解，3名患者（27.3%）病情稳定。
普利妥单抗耐受性良好，每周高达16.2mg/kg未观察到剂量限制毒性。有必要进一步研究以确定患者的临床获益情况。
