Posted: Thursday, March 23, 2023
The use of a novel TRK inhibitor in subjects with NTRK fusion–positive, advanced or metastatic solid tumors (currently known as PBI-200) is the focus of a first-in-human, phase I/II open-label, multicenter, dose-escalation, safety, pharmacokinetics, and biomarker study. This ongoing study (ClinicalTrials.gov identifier NCT04901806), which is expected to be completed in June 2024, is being conducted in two phases. This agent received an Orphan Drug designation from the U.S. Food and Drug Administration in July 2022.
The study is aiming to recruit 74 patients with NTRK-amplified advanced or metastatic solid tumors or refractory EWSR1-WT1 fusion–positive desmoplastic small round cell tumors. Phase I is the dose-escalation portion of the study, involving the evaluation of safety and tolerability and establishing the recommended phase II dose. Once the recommended phase II dose is established, two dose-expansion cohorts will open to accrual: a nonbrain primary tumor cohort and a primary brain tumor cohort.
The primary aim of the study is to assess the number of patients with adverse events, severity of adverse events, and overall response rates. The secondary endpoints include plasma drug concentration time, overall response rate, duration of response, and progression-free survival. Patients in the nonbrain primary tumor cohort will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST), and patients in the primary brain tumors cohort will be assessed by Response Assessment in Neuro-Oncology (RANO) criteria.
Initially, the dose-escalation portion of the study will enroll single-subject cohorts until a patient has a grade 2 or higher adverse event, at which time a 3+3 design will be employed. During the phase I dose-escalation and phase II dose-expansion cohorts, PBI-200 will be administered orally over continuous 28-day cycles. Thereafter, dose escalation will continue until the maximum tolerated dose is reached or the recommended phase II dose is established.
U.S. National Library of Medicine