Placental growth factor (PlGF) and its receptor neuropilin 1 are increased in malignant embryonal tumors and drive tumor progression by boosting cell proliferation, survival, and metastasis. In orthotopic models of medulloblastoma, the blocking monoclonal antibody TB-403 acts against PlGF to slow the growth of tumors and enhance the number of patients who survive their disease. Researchers carried out a phase I, open-label, multicenter, dose-escalation study of TB-403 in pediatric patients who had cancer that had returned or was resistant to treatment. In the trial, a total of 4 different dose levels (20 mg/kg, 50 mg/kg, 100 mg/kg, and 175 mg/kg) were administered utilizing a 3 + 3 strategy for dose escalation. Subjects received 2 doses of TB-403 (days 1 and 15) every cycle. After cycle 1, temozolomide or etoposide could be introduced. The primary objective was to determine the maximum tolerated dosage (MTD) of TB-403 monotherapy during a dose-limiting toxicity assessment period. The secondary and exploratory aims included effectiveness, medication pharmacokinetics, and identification of pharmacodynamic biomarkers. About 15 participants were treated in 4 dose levels. All subjects got 2 doses of TB-403 in cycle 1. However, the maximum tolerated dose (MTD) was not accomplished despite the fact that 5 significant treatment-emergent adverse events were documented in 3 patients. While no full or partial responses were detected, 7 of 11 relapsed participants with medulloblastoma sustained stable disease, which continued for more than 100 days in 4 of 7 subjects. TB-403 was safe and well tolerated at all dose levels. No MTD was reached. The findings appear promising, and as a result, there is a need for additional research into the drug’s effectiveness in treating medulloblastoma in young patients.

 

Source: aacrjournals.org/clincancerres/article-abstract/28/18/3950/708998/A-Phase-I-Trial-of-TB-403-in-Relapsed?redirectedFrom=fulltext