A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) in Pediatric and Young Adult Participants With Solid Tumors

Phase 1

Terminated

Conditions: Solid Tumor

Interventions: Drug: Atezolizumab

Registration Number: NCT02541604

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This early phase, multicenter, open-label, single-arm study evaluated the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of atezolizumab in pediatric and young adult participants with solid tumors for which prior treatment was proven to be ineffective.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 87

Inclusion Criteria

Pediatric solid tumor (including Hodgkin's and Non-Hodgkin's lymphoma), for which prior treatment had proven to be ineffective (that is, relapsed or refractory) or intolerable
Disease that is measurable as defined by RECIST v1.1, mINRC, Revised Response Criteria for Malignant Lymphoma, RANO criteria (as appropriate) or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures
Archival tumor tissue block or 15 freshly cut, unstained, serial slides available for submission, or willingness to undergo a core or excisional biopsy prior to enrollment (fine-needle aspiration, brush biopsy, and lavage samples are not acceptable).

Participants with fewer than 15 slides available may be eligible for study entry following discussion with Medical Monitor

Lansky Performance Status (participants less than [<] 16 years old) or Karnofsky Performance Status (participants greater than or equal to [>=] 16 years old) >=50
Life expectancy >=3 months, in the investigator's judgment
Adequate hematologic and end organ function, confirmed by laboratory results obtained within 28 days prior to initiation of study drug

Exclusion Criteria

Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, except ATRT
Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
Prior allogeneic hematopoietic stem-cell transplantation or prior solid-organ transplantation
Treatment with chemotherapy (other than high-dose chemotherapy as described above) or differentiation therapy (such as retinoic acid) or immunotherapy (such as anti-GD2 antibody treatment) within 3 weeks prior to initiation of study drug or, if treatment included nitrosoureas, within 6 weeks prior to initiation of study drug
Treatment with thoracic or mediastinal radiotherapy within 3 weeks prior to initiation of study drug
Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives) or biologic therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to initiation of study drug. This requirement may be waived at the investigator's request if the participant has recovered from therapeutic toxicity to the degree specified in the protocol, with approval of the Medical Monitor
Treatment with a long-acting hematopoietic growth factor within 2 weeks prior to initiation of study drug or a short-acting hematopoietic growth factor within 1 week prior to initiation of study drug
Treatment with investigational therapy (with the exception of cancer therapies as described above) within 4 weeks prior to initiation of study drug
Treatment with a live vaccine or a live, attenuated vaccine (e.g., nasal spray of live attenuated influenza vaccine or FluMist®) within 4 weeks prior to initiation of study drug or anticipation that such treatment will be required during the study or within 5 months after the final dose of study drug
Treatment with herbal cancer therapy within 1 week prior to initiation of study drug
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin 2 [IL-2]) within 6 weeks or five drug elimination half-lives prior to Day 1 of Cycle 1, whichever is longer
Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) at the time of initiation of study drug, or anticipated requirement for systemic immunosuppressive medications during the study
Current treatment with therapeutic anticoagulants
Any non-hematologic toxicity (excluding alopecia) from prior treatment that has not resolved to Grade less than or equal to (<=) 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) at screening
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atezolizumab	Atezolizumab	Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams \[mg\]) on Day 1 of each 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Minimum Serum Concentration (Cmin) of Atezolizumab	PRD (0 hr) on D1 of Cy2,3,4,8, 12, 16 (1 Cy=21 days) and every 8 cycles thereafter; at any time during visit at study drug discontinuation visit, at least 90 days (maximum 150 days) after the last dose of study drug (up to approximately 42 months)
Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)	Note: In Cohort 5, the response was observed in a rhabdoid tumor. Participant was erroneously enrolled in the Non-rhabdomyosarcoma soft tissue sarcoma cohort.
PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest	From baseline up to approximately 42 months
Maximum Serum Concentration (Cmax) of Atezolizumab	Predose (PRD; 0 hours [hr]), 0.5 hr post-infusion (P-I; infusion duration=30-60 minutes) on Day (D) 1 of Cycle (Cy) 1 and 4 (1 Cy=21 days)
Atezolizumab Serum Concentration at Washout	At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
Area Under the Concentration-Time Curve (AUC) of Atezolizumab	PRD (0 hr), 0.5 hr P-I (infusion duration=30-60 minutes) on D1 of Cy1; at any time during visit on Cy1D8 (1 Cy=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab	PRD (0 hr) on D1 of Cy1,2,3,4,8,12,16 (1 Cy=21 days) & every 8 cycles thereafter; at any time during visit on Cy1D8, study drug discontinuation, at least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Secondary Outcome Measures

Name	Time	Method
DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Optimal Dose of Atezolizumab in Pediatric Adult Participants	From baseline up to approximately 42 months	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
Overall Survival (OS)	Baseline until death (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Optimal Dose of Atezolizumab in Young Adult Participants	From baseline up to approximately 42 months	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Trial Locations

Locations (30): Universitäts-Kinderspital; Abteilung für Onkologie
🇨🇭
Zürich, Switzerland
Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica
🇮🇹
Padova, Veneto, Italy
Hospital Sant Joan De Deu
🇪🇸
Esplugues De Llobregas, Barcelona, Spain
Rigshospitalet; BØRNEUNGEKLINIKKEN, Ambulatoriet for kræft- og Blodsygdomme hos børn og unge
🇩🇰
København Ø, Denmark
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Klinik Johann Wolfgang von Goethe Uni
🇩🇪
Frankfurt, Germany
Alberta Children'S Hospital
🇨🇦
Calgary, Alberta, Canada
Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique
🇫🇷
Lyon, France
Schneider Children's Medical Center
🇮🇱
Petach-Tikva, Israel
Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica
🇮🇹
Milano, Lombardia, Italy
Hospital Infantil Universitario Nino Jesus
🇪🇸
Madrid, Spain
Stanford University/Lucile Packard Children's Hospital
🇺🇸
Palo Alto, California, United States
Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
🇮🇹
Torino, Piemonte, Italy
Arkansas Children'S Hospital
🇺🇸
Little Rock, Arkansas, United States
IRCCS Istituto Giannina Gaslini; Unità Operativa Oncologica Pediatrica
🇮🇹
Genova, Liguria, Italy
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica
🇮🇹
Roma, Lazio, Italy
Erasmus MC / location Sophia Kinderziekenhuis
🇳🇱
Rotterdam, Netherlands
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Institut Curie, Oncologie Pédiatrique
🇫🇷
Paris, France
Institut Gustave Roussy; Service Pediatrique
🇫🇷
Villejuif, France
Birmingham Children's Hospital
🇬🇧
Birmingham, United Kingdom
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Bristol Royal Hospital For Children
🇬🇧
Bristol, United Kingdom
Leeds General Infirmary; Paediatric Oncology & Haematology
🇬🇧
Leeds, United Kingdom
The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
🇬🇧
Newcastle Upon Tyne, United Kingdom
Royal Marsden Hospital; Pediatric Unit
🇬🇧
Surrey, United Kingdom
Penn State Milton S. Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States