A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumours

Official Title

A Phase I/II, Multicentre, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumours

Summary:

This is a Phase I/II, multicentre, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumours.

This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumours to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.

Trial Description

Primary Outcome:

• Number of Participants with at Least One Adverse Event, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
• Number of Participants with Dose-Limiting Toxicities (DLTs)
• Parts 2 and 3: Percentage of Participants with TP53 Wild-Type (WT) Neuroblastoma Achieving an Objective Response
• Parts 2 and 3: Complete Remission Rate Within 2 Cycles of Study Treatment in Participants with TP53 WT Leukemia
• Parts 2 and 3: Percentage of Participants with TP53 WT ALL who are Minimal Residual Disease (MRD)-Negative Within 2 Cycles of Study Treatment

• Clinical Benefit Rate (CBR) in Participants with Solid Tumours (Including Neuroblastoma)
• Duration of Objective Response in Participants with Solid Tumours (Including Neuroblastoma)
• Progression-Free Survival in Participants with Solid Tumours (Including Neuroblastoma)
• Percentage of Participants with Solid Tumours (Including Neuroblastoma) Achieving an Objective Response Irrespective of TP53 Mutation Status
• Overall Survival
• Number of Participants with Leukemia Receiving Transplant After Study Treatment
• Duration of Objective Response in Participants with Leukemia
• Event-Free Survival in Participants with Leukemia
• Complete Remission Rate in Participants with Leukemia Irrespective of TP53 Mutation Status
• Percentage of Participants with TP53 WT AML who are MRD-Negative Within 2 Cycles of Study Treatment
• Plasma Concentration of Idasanutlin Over Time, as a Single Agent and in Combination with Chemotherapy or Venetoclax
• Plasma Concentration of Venetoclax Over Time

View this trial on ClinicalTrials.gov