search
Back to results

Phase I/II Study of Avelumab in Pediatric Cancer Subjects

Primary Purpose

Refractory or Relapsed Solid Tumors, Lymphoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Avelumab
Avelumab
Sponsored by
EMD Serono Research & Development Institute, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory or Relapsed Solid Tumors focused on measuring Avelumab, Anti PD-L1, Solid tumors, CNS tumors, Lymphoma, Pediatric subjects

Eligibility Criteria

0 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female subjects 0 to less than 18 years of age at the time of first treatment dose with histologically or cytologically confirmed solid malignant tumors (including CNS tumors) or lymphoma for which no standard therapy is available
  • Confirmed progression on or refractory to standard therapy or no standard therapy available.
  • Availability of archival formalin-fixed, paraffin-embedded block containing tumor tissue, or slides, or a fresh/recent tumor biopsy prior to avelumab treatment for subjects in Phase 2
  • Adequate bone marrow, kidney, and liver function
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
  • Concurrent anticancer treatment or immunosuppressive agents
  • Prior organ transplantation
  • Significant acute or chronic infections
  • Other significant diseases or conditions that might impair the subject's tolerance of trial treatment
  • Other protocol defined exclusion criteria could apply

Sites / Locations

  • Children's Hospital Colorado
  • The Children's Hospital at Montefiore (CHAM)
  • Cliniques Universitaires Saint-Luc
  • UZ Leuven
  • Children's Hospital - London Health Sciences Centre
  • CHU Sainte-Justine
  • The Hospital for Sick Children
  • Rigshospitalet
  • Samsung Medical Center
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1: Avelumab

Phase 2, Cohort 1: Avelumab

Phase 2, Cohort 2: Avelumab

Arm Description

Outcomes

Primary Outcome Measures

Phase 1: Occurrence and Severity of Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03)
Phase 1: Occurrence of Dose Limiting Toxicity
Phase 2: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator

Secondary Outcome Measures

Phase 1: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Phase 1 and Phase 2: Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Phase 1 and Phase 2: Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Phase 1 and Phase 2: Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Phase 1 and Phase 2: Overall Survival (OS) Time
Phase 1 and Phase 2: Occurrence and Severity of Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest, and Treatment-Related AEs, According to the NCI-CTCAE Version 4.03
Phase 1 and Phase 2: Incidence of Laboratory Abnormalities as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab
Phase 1 and Phase 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Avelumab
Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab
Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab
Phase 1 and Phase 2: Immunogenicity as measured by Incidence of Antidrug Antibody (ADA) and Neutralizing Antibody (Nabs)
Phase 1 and Phase 2: Tumor Programmed Death Ligand 1 (PD-L1) Expression Levels
Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels
Phase 1 and Phase 2: T-cell Population in Blood
Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood
Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations
Phase 1 and Phase 2: Body Temperature
Phase 1 and Phase 2: Heart Rate
Phase 1 and Phase 2: Respiratory Rate
Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure

Full Information

First Posted
February 26, 2018
Last Updated
December 3, 2021
Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
search

1. Study Identification

Unique Protocol Identification Number
NCT03451825
Brief Title
Phase I/II Study of Avelumab in Pediatric Cancer Subjects
Official Title
Open-label, Phase I/II Study to Evaluate Pharmacokinetics, Pharmacodynamics, Safety, and Anticancer Activity of Avelumab in Pediatric Subjects From Birth to Less Than 18 Years of Age With Refractory or Relapsed Solid Tumors and Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
March 7, 2018 (Actual)
Primary Completion Date
July 27, 2021 (Actual)
Study Completion Date
July 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a multi-center, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in pediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumors (including central nervous system tumors) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy. The study was planned to be conducted in 2 parts: the dose-finding part (Phase I) and the tumor-specified expansion part (Phase II). However, Phase II was cancelled due to limited clinical benefit of PD-L1 monotherapy in pediatric participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory or Relapsed Solid Tumors, Lymphoma
Keywords
Avelumab, Anti PD-L1, Solid tumors, CNS tumors, Lymphoma, Pediatric subjects

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: Avelumab
Arm Type
Experimental
Arm Title
Phase 2, Cohort 1: Avelumab
Arm Type
Experimental
Arm Title
Phase 2, Cohort 2: Avelumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Avelumab
Intervention Description
Subjects will receive avelumab administered intravenously (IV) once every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Avelumab
Intervention Description
Subjects will receive avelumab at a recommended phase II dose (RP2D) adjudicated by a safety monitoring committee (SMC) from phase I part of the study.
Primary Outcome Measure Information:
Title
Phase 1: Occurrence and Severity of Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03)
Time Frame
From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 13 months)
Title
Phase 1: Occurrence of Dose Limiting Toxicity
Time Frame
Day 1 up to Day 28
Title
Phase 2: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time Frame
Time from first dose until confirmed disease progression assessed up to maximum of 48 months
Secondary Outcome Measure Information:
Title
Phase 1: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time Frame
Time from first dose until confirmed disease progression assessed up to maximum of 48 months
Title
Phase 1 and Phase 2: Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time Frame
Time from first documented complete response (CR) or partial response (PR) to the date of first documentation of Progressive disease (PD) or death, assessed up to maximum of 48 months
Title
Phase 1 and Phase 2: Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time Frame
Time from first dose up to first documented CR or PR, assessed up to maximum of 48 months
Title
Phase 1 and Phase 2: Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time Frame
Time from first dose up to the date of first documented disease progression or death due to any cause, assessed up to maximum of 48 months
Title
Phase 1 and Phase 2: Overall Survival (OS) Time
Time Frame
Time from first dose until death, assessed up to maximum of 48 months
Title
Phase 1 and Phase 2: Occurrence and Severity of Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest, and Treatment-Related AEs, According to the NCI-CTCAE Version 4.03
Time Frame
From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 48 months)
Title
Phase 1 and Phase 2: Incidence of Laboratory Abnormalities as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Avelumab
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Immunogenicity as measured by Incidence of Antidrug Antibody (ADA) and Neutralizing Antibody (Nabs)
Time Frame
Baseline up to 30 days after the last dose (assessed maximum up to 48 months)
Title
Phase 1 and Phase 2: Tumor Programmed Death Ligand 1 (PD-L1) Expression Levels
Time Frame
Baseline and at disease progression (assessed up to maximum of 48 months)
Title
Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: T-cell Population in Blood
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Body Temperature
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Heart Rate
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Respiratory Rate
Time Frame
Baseline up to 48 months
Title
Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure
Time Frame
Baseline up to 48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects 0 to less than 18 years of age at the time of first treatment dose with histologically or cytologically confirmed solid malignant tumors (including CNS tumors) or lymphoma for which no standard therapy is available Confirmed progression on or refractory to standard therapy or no standard therapy available. Availability of archival formalin-fixed, paraffin-embedded block containing tumor tissue, or slides, or a fresh/recent tumor biopsy prior to avelumab treatment for subjects in Phase 2 Adequate bone marrow, kidney, and liver function Other protocol defined inclusion criteria could apply Exclusion Criteria: Prior therapy with any antibody or drug targeting T-cell coregulatory proteins Concurrent anticancer treatment or immunosuppressive agents Prior organ transplantation Significant acute or chronic infections Other significant diseases or conditions that might impair the subject's tolerance of trial treatment Other protocol defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
The Children's Hospital at Montefiore (CHAM)
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
Children's Hospital - London Health Sciences Centre
City
London
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montréal
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Citations:
PubMed Identifier
35484319
Citation
Vugmeyster Y, Grisic AM, Brockhaus B, Rueckert P, Ruisi M, Dai H, Khandelwal A. Avelumab Dose Selection for Clinical Studies in Pediatric Patients with Solid Tumors. Clin Pharmacokinet. 2022 Jul;61(7):985-995. doi: 10.1007/s40262-022-01111-8. Epub 2022 Apr 29.
Results Reference
derived
PubMed Identifier
35262780
Citation
Loeb DM, Lee JW, Morgenstern DA, Samson Y, Uyttebroeck A, Lyu CJ, Van Damme A, Nysom K, Macy ME, Zorzi AP, Xiong J, Pollert P, Joerg I, Vugmeyster Y, Ruisi M, Kang HJ. Avelumab in paediatric patients with refractory or relapsed solid tumours: dose-escalation results from an open-label, single-arm, phase 1/2 trial. Cancer Immunol Immunother. 2022 Oct;71(10):2485-2495. doi: 10.1007/s00262-022-03159-8. Epub 2022 Mar 9.
Results Reference
derived
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS100070-0306
Description
Trial Awareness and Transparency website
URL
https://medical.emdserono.com/en_US/home.html
Description
US Medical Information website, Medical Resources

Learn more about this trial

Phase I/II Study of Avelumab in Pediatric Cancer Subjects

We'll reach out to this number within 24 hrs