KEY TAKEAWAYS
- The phase I trial aimed to evaluate the safety and pharmacokinetics of pritumumab in brain cancer.
- The study included patients (age ≥18) with confirmed CNS cancer who had failed prior standard therapy.
- The study found that pritumumab was safe up to 16.2 mg/kg every 7 days in brain tumor patients.
Pritumumab is a human antibody that targets ectodomain vimentin (EDV), overexpressed in glioblastomas (GBM), making it an ideal immunotherapy target. Researchers aimed to evaluate the safety and pharmacokinetics of pritumumab in brain cancer.
Patients with central nervous system (CNS) cancer who failed prior therapy (excluding insufficient time from prior therapy (<28 days cytotoxic, <14 days non-cytotoxic investigational, <7 days non-cytotoxic/immunotherapy) were given pritumumab in increasing doses, 5 cohorts (1.6 mg/kg to 16.2 mg/kg), on a weekly 3+3 dosing schedule based on dose-limiting toxicities (DLT) encountered through day 28 of treatment to assess safety and pharmacokinetics.
Out of 24 patients,15 received the investigational agent. Among them, 12 had GBM, while one patient had anaplastic astrocytoma, oligodendroglioma, and non-small lung cancer with brain metastases. About 13 patients discontinued treatment due to disease progression, one due to PI discretion for an unrelated CNS infection, and one withdrew for personal reasons. One patient showed a partial response with a substantial reduction of nearly 98.0% and 40.8% in two tumor lesions, and this response lasted for 17 months. There were no dose-limiting toxicities observed for this natural human IgG monoclonal antibody. Adverse events attributed to pritumumab were fatigue (53.3%) and constipation (33.3%). Other rare side effects of pritumumab (6.7%) were nausea, joint tenderness, dehydration, hypomagnesemia, neuropathy, pruritus, scalp dryness, dry skin (face), and depression. There were no grade 3, 4, or 5 adverse events. Preliminary PK data depicted the volume of distribution of 38.36 mL/kg, clearance of 0.1305 mL/h/kg, and half-life of 12.5 days.
The study found that pritumumab was safe up to 16.2 mg/kg every 7 days in brain tumor patients. Phase 2 trials are scheduled to investigate its efficacy independently and with checkpoint inhibitors for recurrent and newly diagnosed gliomas.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04396717
Jose Arganda Carrillo, Santosh Kesari, Jaya Mini Gill, Charles Redfern, Sean Carrick, and Ivan Babic. DOI: 10.1200/JCO.2023.41.16_suppl.2053 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 2053-2053.
