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

NCT02541604 | Terminated Phase 1 Results DMC

• 2 other identifiers: GO296642014-004697-41
• Study Type: interventional
• Target: 87
• Locations: 11 countries
• Sites: 30

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (15)

• 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

  Note: In Cohort 5, the response was observed in a rhabdoid tumor. Participant was erroneously enrolled in the Non-rhabdomyosarcoma soft tissue sarcoma cohort.

  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 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)

• 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)

• 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)

• 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 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)

• 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)

• 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)

Secondary Outcomes (16)

• 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 mINRC in 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 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)

• 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)

• Overall Survival (OS)

  Baseline until death (up to approximately 42 months)

Study Arms (1)

Atezolizumab

EXPERIMENTAL

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

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab was administered as IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle.

Also known as: RO5541267; MPDL3280A; Tecentriq

Atezolizumab

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (30)

Arkansas Children'S Hospital

Little Rock, Arkansas, 72202, United States

Location

Stanford University/Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Rigshospitalet; BØRNEUNGEKLINIKKEN, Ambulatoriet for kræft- og Blodsygdomme hos børn og unge

København Ø, 2100, Denmark

Location

Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique

Lyon, 69373, France

Location

Institut Curie, Oncologie Pédiatrique

Paris, 75231, France

Location

Institut Gustave Roussy; Service Pediatrique

Villejuif, 94805, France

Location

Klinik Johann Wolfgang von Goethe Uni

Frankfurt, 60590, Germany

Location

Schneider Children's Medical Center

Petah Tikva, 49100, Israel

Location

Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica

Rome, Lazio, 00165, Italy

Location

IRCCS Istituto Giannina Gaslini; Unità Operativa Oncologica Pediatrica

Genoa, Liguria, 16147, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica

Padua, Veneto, 35128, Italy

Location

Erasmus MC / location Sophia Kinderziekenhuis

Rotterdam, 3015 GJ, Netherlands

Location

Hospital Sant Joan De Deu

Esplugues de Llobregas, Barcelona, 08950, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Universitäts-Kinderspital; Abteilung für Onkologie

Zurich, 8032, Switzerland

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital For Children

Bristol, BS2 8BJ, United Kingdom

Location

Leeds General Infirmary; Paediatric Oncology & Haematology

Leeds, LS1 3EX, United Kingdom

Location

The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Royal Marsden Hospital; Pediatric Unit

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (3)

• Nabbi A, Danesh A, Espin-Garcia O, Pedersen S, Wellum J, Fu LH, Paulson JN, Geoerger B, Marshall LV, Trippett T, Rossato G, Pugh TJ, Hutchinson KE. Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab. Nat Cancer. 2023 Apr;4(4):502-515. doi: 10.1038/s43018-023-00534-x. Epub 2023 Apr 10.

  PMID: 37038005 DERIVED

• 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.

  PMID: 31780255 DERIVED

• 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.

  PMID: 31753029 DERIVED

MeSH Terms

Interventions

atezolizumab

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: September 4, 2015
• Study Start: November 30, 2015
• Primary Completion: June 6, 2019
• Study Completion: June 6, 2019
• Last Updated: February 25, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Locations

CA (1); DK (1); IL (1); DE (1); IT (5); FR (3); US (7); ES (4); NL (1); GB (5); CH (1)