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

NCT05081180 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MS100070_00872020-004397-222024-512940-51-00
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 9

Brief 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) tumors.

Conditions

Central Nervous System Tumors

Keywords

Avelumab; Lenvatinib; Tumors; Pediatric CNS tumors

Outcome Measures

Primary Outcomes (3)

• 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

  up to 857 days

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

  Baseline (Day 1) up to Day 28

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

  until progressive disease or death, assessed up to Day 1534

Secondary Outcomes (25)

• 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

  up to 876 days

• 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

  up to 876 days

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

  up to 876 days

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

  up to 876 days

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

  up to 876 days

Study Arms (1)

Avelumab + Lenvatinib

EXPERIMENTAL

Drug: Avelumab; Drug: Lenvatinib

Interventions

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.

Avelumab + Lenvatinib

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.

Avelumab + Lenvatinib

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: collaborator
• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (9)

CHU Sainte-Justine

Montreal, Canada

Location

The Hospital for Sick Children

Toronto, Canada

Location

CHU Angers - Hôpital Hôtel Dieu - Service de Cancérologie Pédiatrique

Angers, France

Location

Hôpital de la Timone

Marseille, France

Location

Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris

Paris, France

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, Germany

Location

Universitaetsklinikum Muenster

Münster, Germany

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neoplasms

Interventions

avelumab; lenvatinib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: October 18, 2021
• Study Start: December 3, 2021
• Primary Completion: February 11, 2026
• Study Completion (Estimated): May 29, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); DE (2); KR (2); FR (3)