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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02541604
• Other study ID #: GO29664
• Secondary ID: 2014-004697-41
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 30, 2015
• Est. completion date: June 6, 2019

Study information

• Verified date: February 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 87
• Est. completion date: June 6, 2019
• Est. primary completion date: June 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
Canada	Alberta Children'S Hospital	Calgary	Alberta
Denmark	Rigshospitalet; BØRNEUNGEKLINIKKEN, Ambulatoriet for kræft- og Blodsygdomme hos børn og unge	København Ø
France	Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique	Lyon
France	Institut Curie, Oncologie Pédiatrique	Paris
France	Institut Gustave Roussy; Service Pediatrique	Villejuif
Germany	Klinik Johann Wolfgang von Goethe Uni	Frankfurt
Israel	Schneider Children's Medical Center	Petach-Tikva
Italy	IRCCS Istituto Giannina Gaslini; Unità Operativa Oncologica Pediatrica	Genova	Liguria
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica	Milano	Lombardia
Italy	Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica	Padova	Veneto
Italy	Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica	Roma	Lazio
Italy	Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino	Torino	Piemonte
Netherlands	Erasmus MC / location Sophia Kinderziekenhuis	Rotterdam
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Universitäts-Kinderspital; Abteilung für Onkologie	Zürich
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	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 States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Arkansas Children'S Hospital	Little Rock	Arkansas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stanford University/Lucile Packard Children's Hospital	Palo Alto	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest		From baseline up to approximately 42 months
Primary	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)
Primary	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)
Primary	Atezolizumab Serum Concentration at Washout		At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Overall Survival (OS)		Baseline until death (up to approximately 42 months)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Optimal Dose of Atezolizumab in Pediatric Adult Participants	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.	From baseline up to approximately 42 months
Secondary	Optimal Dose of Atezolizumab in Young Adult Participants	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.	From baseline up to approximately 42 months