Clinical trial NCT02541604: 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
Official title: An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-04
Enrollment: 87
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: 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)
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors
timeFrame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
timeFrame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
timeFrame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT
timeFrame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
timeFrame: From baseline up to approximately 42 months
measure: Maximum Serum Concentration (Cmax) of Atezolizumab
timeFrame: 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)
measure: Minimum Serum Concentration (Cmin) of Atezolizumab
timeFrame: 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)
measure: Atezolizumab Serum Concentration at Washout
timeFrame: At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
measure: Area Under the Concentration-Time Curve (AUC) of Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: 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)
Secondary outcomes:
measure: Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: Overall Survival (OS)
timeFrame: Baseline until death (up to approximately 42 months)
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: 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
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
timeFrame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
measure: Optimal Dose of Atezolizumab in Pediatric Adult Participants
timeFrame: From baseline up to approximately 42 months
measure: Optimal Dose of Atezolizumab in Young Adult Participants
timeFrame: From baseline up to approximately 42 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children'S Hospital
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford University/Lucile Packard Children's Hospital
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Calgary
country: Canada
facility: Alberta Children'S Hospital
state: Alberta
city: København Ø
country: Denmark
facility: Rigshospitalet; BØRNEUNGEKLINIKKEN, Ambulatoriet for kræft- og Blodsygdomme hos børn og unge
city: Lyon
country: France
facility: Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique
city: Paris
country: France
facility: Institut Curie, Oncologie Pédiatrique
city: Villejuif
country: France
facility: Institut Gustave Roussy; Service Pediatrique
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini; Unità Operativa Oncologica Pediatrica
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
state: Piemonte
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica
state: Veneto
city: Rotterdam
country: Netherlands
facility: Erasmus MC / location Sophia Kinderziekenhuis
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Zürich
country: Switzerland
facility: Universitäts-Kinderspital; Abteilung für Onkologie
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital For Children
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary; Paediatric Oncology & Haematology
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
city: Surrey
country: United Kingdom
facility: Royal Marsden Hospital; Pediatric Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Geoerger B, Zwaan CM, Marshall LV, Michon J, Bourdeaut F, Casanova M, Corradini N, Rossato G, Farid-Kapadia M, Shemesh CS, Hutchinson KE, Donaldson F, Liao M, Caron H, Trippett T. Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Lancet Oncol. 2020 Jan;21(1):134-144. doi: 10.1016/S1470-2045(19)30693-X. Epub 2019 Nov 25.
citation: Shemesh CS, Chanu P, Jamsen K, Wada R, Rossato G, Donaldson F, Garg A, Winter H, Ruppel J, Wang X, Bruno R, Jin J, Girish S. Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer. J Immunother Cancer. 2019 Nov 21;7(1):314. doi: 10.1186/s40425-019-0791-x.