A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer

Official Title

A Phase 1/2 Study of the TRK Inhibitor Selitrectinib in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Summary:

This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.

Trial Description

Primary Outcome:

• Phase 1: Maximum tolerated dose (MTD)
• Phase 1: Recommended dose
• Phase 2: Overall response rate (ORR) for patients <12 years from Cohort 1 by IRR
• Phase 2: Overall response rate (ORR) for patient ≥12 years from Cohort 1 by IRR

Secondary Outcome:

• Phase 1: Incidence of adverse events
• Phase 1: Severity of adverse events
• Phase 1: Duration of adverse events
• Phase 1: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
• Phase 1: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
• Phase 1: Overall response rate (ORR) in patients with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator
• Phase 1: Overall response rate (ORR) in patients with primary central nervous system (CNS) malignancies determined by investigator
• Phase 1: Overall survival (OS)
• Phase 1: Maximum concentration of BAY2731954 in plasma (Cmax)
• Phase 1: Area under the concentration versus time curve of BAY2731954 in plasma (AUC(0-last))
• Phase 2: Incidence of adverse events in patients ≥12 years
• Phase 2: Severity of adverse events in patients ≥12 years
• Phase 2: Duration of adverse events in patients ≥12 years
• Phase 2: Incidence of adverse events in patients <12 years
• Phase 2: Severity of adverse events in patients <12 years
• Phase 2: Duration of adverse events in patients <12 years
• Phase 2: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
• Phase 2: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
• Phase 2: Overall response rate (ORR) in Cohort 2 determined by IRR
• Phase 2: Overall response rate (ORR) determined by investigator
• Phase 2: Duration of response (DOR) determined by IRR
• Phase 2: Duration of response (DOR) determined by investigator
• Phase 2: Progression free survival (PFS) determined by IRR
• Phase 2: Progression free survival (PFS) determined by investigator
• Phase 2: Overall survival (OS)
• Phase 2: Clinical benefit rate (CBR) determined by IRR
• Phase 2: Clinical benefit rate (CBR) determined by investigator

The trial will be conducted in 2 parts: dose escalation (Phase 1) and dose expansion (Phase 2) . The primary objective of Phase 1 is to establish the recommended dose of selitrectinib to treat neurotrophic tyrosine kinase (NTRK) fusion cancers in patients a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase 1 are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumours. The primary objective of Phase 2 is to assess the overall response rate in NTRK fusion cancer patients as determined by an independent radiology committee (IRR). Secondary objectives of Phase 2 comprise the safety and efficacy of selitrectinib at the recommended dose.

View this trial on ClinicalTrials.gov