A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumours

Official Title

A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumours

Summary:

This is an open-label, multi-centre Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumour.

Trial Description

Primary Outcome:

• To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumours: Dose Limiting Toxicities (DLTs)
• To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumours: DLTs
• Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 per Independent Review Committee (IRC)
• ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC

Secondary Outcome:

• Plasma Concentrations of LOXO-292
• Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292
• Maximum Concentration (Cmax) of LOXO-292
• Time to Maximum Concentration (Tmax) of LOXO-292
• Recommended LOXO-292 Dose for Phase 2 (MTD)
• To Assess the Preliminary Anti-Tumour Activity of LOXO-292 in Pediatric Participants with Tumours Harboring an Activating RET Alteration as Determined by ORR Based on RECIST v1.1
• Changes from Baseline in Pain Measures as Measured by Wong Baker Faces scales. Wong-Baker Faces Pain Scale includes pictures of facial expressions with correlating scores of 0 being 'no hurt' and 10 being 'hurts worst'.
• Changes from Baseline in Health Related Quality of Life Measures as Measured by Pediatric Quality of Life (PedsQoL) Inventory Core. PedsQoL includes a list of problems with scores of 0 being 'never a problem' and 4 being 'almost always a problem'.
• Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
• Objective Response Rate as Assessed by RANO, as Assessed by Investigator
• Duration of Response (DOR) as Assessed by Investigator
• Duration of Response (DOR) as Assessed by the IRC
• Progression Free Survival (PFS) as Assessed by Investigator
• PFS as Assessed by IRC
• Overall survival (OS)
• Clinical Benefit Rate (by Investigator)
• Clinical Benefit Rate (by IRC)
• Frequency of Adverse Events (AEs)
• To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumour with Diagnostic Tests Being Evaluated by Sponsor
• Phase 2: Post-Operative Stage on Participants Treated with LOXO-292
• Phase 2: Surgical Margin Status in Participants Treated with LOXO-292
• Descriptive Analysis of Pretreatment Surgical Plan
• Descriptive Analysis of Post-Treatment Plans

This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, participants will be enrolled using a rolling 6 dose escalation scheme. The starting dose of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice a day (BID). Once the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is identified, participants will be enrolled to one of four phase 2 dose expansion cohorts depending on tumour histology and tumour genotype. Cycle length will be 28 days.

View this trial on ClinicalTrials.gov