Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumours

Official Title

Single-arm, Multicentre Phase I/Ib Study of Avelumab + Lenvatinib in Children With Primary CNS Tumours

Summary:

This study consists of 2 parts: Dose Escalation Part 1 and Dose Expansion Part 2. The Dose Escalation Part 1 will evaluate the safety and tolerability of Avelumab in combination with Lenvatinib and determine the recommended Avelumab and Lenvatinib dose for expansion. Dose Expansion Part 2 will assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary central nervous system (CNS) tumours.

Trial Description

Primary Outcome:

• Dose Escalation Part 1: Number of Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater Than or Equal to (>=) 3 Treatment-emergent Adverse Event (TEAEs) According to National Cancer Institute-CTCAE Version 5.0
• Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
• Dose Expansion Part 2: Progression-free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

• Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths
• Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
• Dose Escalation Part 1: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters
• Dose Escalation Part 1: Objective Response Rate (ORR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators
• Dose Escalation Part 1: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators
• Dose Escalation Part 1: Progression-Free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria
• Dose Escalation Part 1: Overall Survival (OS)
• Dose Escalation Part 1: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab
• Dose Escalation Part 1: Area Under the Serum Concentration-Time Curve From the Time of Dosing 336 Hours (AUC0-336 [hr]) of Avelumab
• Dose Escalation Part 1: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab
• Dose Escalation Part 1: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib
• Dose Escalation Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib
• Dose Escalation (Part 1): Area Under the Plasma Concentration-Time Curve From the Time of Dosing to 24 Hours (AUC0-24 [hr]) of Lenvatinib:
• Dose Escalation Part 1: Immunogenicity of Avelumab as Measured by Antidrug Antibody (ADA) Assay
• Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths
• Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
• Dose Expansion Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters
• Dose Expansion Part 2: Objective Response Rate (ORR) Rate According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators
• Dose Expansion Part 2: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators
• Dose Expansion Part 2: Overall Survival (OS)
• Dose Expansion Part 2: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab
• Dose Expansion Part 2:Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab
• Dose Expansion Part 2: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib
• Dose Expansion Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib
• Dose Expansion Part 2: Immunogenicity of avelumab as measured by ADA assay

View this trial on ClinicalTrials.gov