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NCT Number: NCT05081180

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

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) tumors.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Central Nervous System Tumors Central Nervous System Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms

Age range

2 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

CHU Sainte-Justine, Montreal, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with histologically confirmed diagnosis of primary CNS malignancy as follows: a) Primary CNS tumors: the tumor should be considered high-grade histologically; prior radiotherapy is allowed; participants must have progressed after at least 1 prior systemic therapy, except for those with diffuse midline glioma with or without the H3 K27M mutation. b) Specific for participants with diffuse midline glioma with or without the H3 K27M mutation: prior radiotherapy is allowed; no more than 1 prior systemic therapy is allowed; participants with diffuse midline glioma with or without the H3 K27M mutation who have not received prior systemic therapy but have prior radiotherapy only are allowed to enroll
  • On screening scans, measurable disease by RANO criteria
  • Participants must have a Lansky performance status >= 50 for age <= 16 years or Karnofsky performance status >= 50 for age > 16 years at Screening
  • Other protocol defined inclusion criteria could apply

Exclusion criteria

  • Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and World Health organization (WHO) Grade 1 tumors
  • Participants demonstrating evidence of worsening of neurologic deficit within 1 week prior to initiation of study interventions
  • Participants with bulky tumor, defined as: a) Tumor with any evidence of uncal herniation or midline shift; b) Tumor with a diameter of > 4 centimeters (cm) in 1 dimension on T2/ fluid-attenuated inversion recovery (FLAIR) images; c) Tumor that in the opinion of the Investigator shows significant mass effect
  • Participants are not eligible if they experience uncontrolled seizures, defined as: a) Seizures requiring regular use of rescue medications. b) Seizures requiring increasing doses of antiepileptic medications. c) Seizures that in the opinion of the Investigator compromise the ability of the participant to tolerate study intervention or interfere with study procedures
  • Participants who have received major surgery (including but not limited to neurosurgical resection, brain biopsy, or radiation to the primary brain tumor) within 28 days prior to the first dose of study interventions
  • Participants with history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions
  • Other protocol defined exclusion criteria could apply

Treatment and study plan

Avelumab

Drug

Participants with primary CNS malignancies who have received at least 1 prior therapy will be enrolled into Dose Escalation Part 1 and will receive intravenous infusion at a flat dose or weight based dose of Avelumab, every 2 weeks (Q2W) until progression, unacceptable toxicity, or withdrawal of consent. Enrollment into part 1 of the study will end when Maximum tolerated dose (MTD) and/or a safe Recommended Dose for Expansion (RDE) for the expansion cohort is determined. Participants with defined CNS tumors will be enrolled into Dose Expansion Part 2 and will receive RDE in Part 2 until progression, unacceptable toxicity, or withdrawal of consent.

Lenvatinib

Drug

Participants with primary CNS malignancies who have received at least 1 prior therapy will be enrolled into Dose Escalation Part 1 and will receive daily oral escalated dose level of Lenvatinib until progression, unacceptable toxicity, or withdrawal of consent. Enrollment into part 1 of the study will end when MTD and/or a safe Recommended Dose for Expansion (RDE) for the expansion cohort is determined. Participants with defined CNS tumors will be enrolled into Dose Expansion Part 2 and will receive RDE of Lenvatinib in Part 2 until progression, unacceptable toxicity, or withdrawal of consent.

Primary outcomes

  1. 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

    Time frame: up to 857 days

  2. Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

    Time frame: Baseline (Day 1) up to Day 28

  3. Dose Expansion Part 2: Progression-free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

    Time frame: until progressive disease or death, assessed up to Day 1534

Secondary outcomes

  1. 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

    Time frame: up to 876 days

  2. 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

    Time frame: up to 876 days

  3. Dose Escalation Part 1: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters

    Time frame: up to 876 days

  4. Dose Escalation Part 1: Objective Response Rate (ORR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

    Time frame: up to 876 days

  5. Dose Escalation Part 1: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

    Time frame: up to 876 days

  6. Dose Escalation Part 1: Progression-Free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria

    Time frame: until progressive disease or death, assessed up to 876 days

  7. Dose Escalation Part 1: Overall Survival (OS)

    Time frame: up to 876 days

  8. Dose Escalation Part 1: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days

  9. Dose Escalation Part 1: Area Under the Serum Concentration-Time Curve From the Time of Dosing 336 Hours (AUC0-336 [hr]) of Avelumab

    Time frame: Pre-dose up to 336 hours post-dose, assessed up to approximately 876 days

  10. Dose Escalation Part 1: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days

  11. Dose Escalation Part 1: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days

  12. Dose Escalation Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days

  13. Dose Escalation (Part 1): Area Under the Plasma Concentration-Time Curve From the Time of Dosing to 24 Hours (AUC0-24 [hr]) of Lenvatinib:

    Time frame: Pre-dose up to 24 hours post-dose, assessed up to approximately 876 days

  14. Dose Escalation Part 1: Immunogenicity of Avelumab as Measured by Antidrug Antibody (ADA) Assay

    Time frame: up to 876 days

  15. 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

    Time frame: up to Day 1534

  16. 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

    Time frame: up to Day 1534

  17. Dose Expansion Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters

    Time frame: up to Day 1534

  18. Dose Expansion Part 2: Objective Response Rate (ORR) Rate According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

    Time frame: up to Day 1534

  19. Dose Expansion Part 2: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators

    Time frame: up to Day 1534

  20. Dose Expansion Part 2: Overall Survival (OS)

    Time frame: up to Day 1534

  21. Dose Expansion Part 2: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534

  22. Dose Expansion Part 2:Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534

  23. Dose Expansion Part 2: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534

  24. Dose Expansion Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib

    Time frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534

  25. Dose Expansion Part 2: Immunogenicity of avelumab as measured by ADA assay

    Time frame: up to Day 1534

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Oct 18, 2021
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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