A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

Official Title

A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumour Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations

Summary:

Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumour activity of repotrectinib in pediatric subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.

Trial Description

Primary Outcome:

• Dose limiting toxicities (DLTs) (Phase 1)
• Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
• Overall Response Rate (ORR) (Phase 2)

Secondary Outcome:

• Overall Response Rate (ORR) (Phase 1)
• Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
• Time to response (TTR) (Phase 1 and Phase 2)
• Duration of response (DOR) (Phase 1 and Phase 2)
• Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)
• Central Nervous System Progression-Free Survival (CNS-PFS) (Phase 2)
• Progression-free survival (PFS) (Phase 2)
• Overall survival (OS) (Phase 2)
• Maximum concentration of repotrectinib in plasma (Cmax)
• Area under the concentration versus time curve of repotrectinib in plasma (AUC)

Enrollment of subjects into Phase 1 will proceed concurrently by age as follows:

• Subjects <12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age <12 years old may be enrolled into the Phase 2 part of the study.

• Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment. Phase 1: Approximately 12 pediatric subjects with locally advanced or metastatic solid tumours, including a primary central nervous system (CNS) tumour, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists. Phase 2: Subjects will be enrolled in one of 3 cohorts as follows: Cohort 1: approximately 10-20 subjects with solid tumours characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline. Cohort 2: approximately 23 subjects with solid tumours characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline. Cohort 3: approximately 20 subjects with solid tumours or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2.

View this trial on ClinicalTrials.gov