Phase I/II Study of Avelumab in Pediatric Cancer Subjects

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03451825
• Other study ID #: MS100070-0306
• Secondary ID: 2017-002985-28
• Status: Completed
• Phase: Phase 1
• Start date: March 7, 2018
• Est. completion date: July 27, 2021

Study information

• Verified date: December 2021
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: July 27, 2021
• Est. primary completion date: July 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Refractory or Relapsed Solid Tumors

Intervention

Drug:
• Avelumab
Subjects will receive avelumab administered intravenously (IV) once every 2 weeks.
• Avelumab
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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Canada	Children's Hospital - London Health Sciences Centre	London
Canada	CHU Sainte-Justine	Montréal
Canada	The Hospital for Sick Children	Toronto
Denmark	Rigshospitalet	Copenhagen
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
United States	Children's Hospital Colorado	Aurora	Colorado
United States	The Children's Hospital at Montefiore (CHAM)	Bronx	New York

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 13 months)
Primary	Phase 1: Occurrence of Dose Limiting Toxicity		Day 1 up to Day 28
Primary	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 from first dose until confirmed disease progression assessed up to maximum of 48 months
Secondary	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 from first dose until confirmed disease progression assessed up to maximum of 48 months
Secondary	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 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
Secondary	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 from first dose up to first documented CR or PR, assessed up to maximum of 48 months
Secondary	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 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
Secondary	Phase 1 and Phase 2: Overall Survival (OS) Time		Time from first dose until death, assessed up to maximum of 48 months
Secondary	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		From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 48 months)
Secondary	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		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab		Baseline up to 48 months
Secondary	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		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Immunogenicity as measured by Incidence of Antidrug Antibody (ADA) and Neutralizing Antibody (Nabs)		Baseline up to 30 days after the last dose (assessed maximum up to 48 months)
Secondary	Phase 1 and Phase 2: Tumor Programmed Death Ligand 1 (PD-L1) Expression Levels		Baseline and at disease progression (assessed up to maximum of 48 months)
Secondary	Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: T-cell Population in Blood		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Body Temperature		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Heart Rate		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Respiratory Rate		Baseline up to 48 months
Secondary	Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure		Baseline up to 48 months

External Links

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