A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases

Background. 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. Methods. 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. Results. 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%). Conclusions. 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.