Phase I/II Study of Avelumab in Pediatric Cancer Participants

NCT03451825 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: MS100070-03062017-002985-28
• Study Type: interventional
• Target: 21
• Locations: 5 countries
• Sites: 11

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.

Conditions

Refractory or Relapsed Solid Tumors; Lymphoma

Keywords

Avelumab; Anti PD-L1; Solid tumors; CNS tumors; Lymphoma; Pediatric subjects

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

  Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. Severity of grade 3 or higher TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1 = Mild, Grade 2= Moderate, Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs as per severity with Grade 3 and higher were reported.

  Baseline up to 1182 days

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  For the purpose of dose finding, any of the following AEs occurring during the primary DLT observation period. Hematologic: Grade 4 neutropenia for more than 7 days in duration; Grade greater than or equal to (\>=) 3 neutropenic infection; Grade \>= 3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia \> 7 days and Grade 4 anemia. Nonhematologic: Any Grade \>= 3 toxicity, except for any of the following: Transient (less than or equal to (\<=) 72 hours; Grade 3 flu-like symptoms or fever, which was controlled with medical management; Transient (\<= 72 hours) Grade 3 fatigue, local reactions, headache, nausea, or emesis that resolved to Grade \<= 1 or to Baseline. Grade 3 diarrhea or Grade 3 skin toxicity that resolved to Grade \<= 1 in less than 7 days after medical management (immunosuppressant treatment) had been initiated. Grade \>= 3 amylase or lipase abnormality that was not associated with clinical manifestations of pancreatitis.

  Baseline up to 28 days

Secondary Outcomes (18)

• Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator

  Baseline up to 1182 days

• 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 documentation of objective response up to 1182 days

• Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator

  Time from start of study treatment up to 1182 days

• Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator

  Time from first administration of study drug until the first documentation of PD or death, assessed up to 1182 days

• Overall Survival (OS)

  Time from first administration of study drug up to 1182 days

Study Arms (2)

Avelumab: 10 miligram per kilogram (mg/kg)

EXPERIMENTAL

Drug: Avelumab

Avelumab 20mg/kg

EXPERIMENTAL

Drug: Avelumab

Interventions

Avelumab DRUG

Participants received an intravenous infusion of avelumab 10mg/kg intervention (IV) once every 2 weeks until confirmed progression, death, unacceptable toxicity, or any criterion for withdrawal occurred.

Avelumab: 10 miligram per kilogram (mg/kg)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (11)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

The Children's Hospital at Montefiore (CHAM)

The Bronx, New York, 10467, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Children's Hospital - London Health Sciences Centre

London, Canada

Location

CHU Sainte-Justine

Montreal, Canada

Location

The Hospital for Sick Children

Toronto, Canada

Location

Rigshospitalet

Copenhagen, Denmark

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University

Seoul, South Korea

Location

Related Publications (2)

• 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.

  PMID: 35484319 RESULT

• 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.

  PMID: 35262780 RESULT

Related Links

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

MeSH Terms

Conditions

Lymphoma; Central Nervous System Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 2, 2018
• Study Start: March 7, 2018
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-01

Locations

US (2); CA (3); DK (1); KR (3); BE (2)