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

• ClinicalTrials.gov Identifier: NCT02541604
• Recruitment Status: Terminated
• First Posted: September 4, 2015
• Results First Posted: February 25, 2020
• Last Update Posted: February 25, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: August 18, 2015
• First Posted Date: September 4, 2015
• Results First Submitted Date: November 11, 2019
• Results First Posted Date: February 25, 2020
• Last Update Posted Date: February 25, 2020
• Actual Study Start Date: November 30, 2015
• Actual Primary Completion Date: June 6, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 24, 2020)

• 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 [ Time Frame: 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.
• 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From baseline up to approximately 42 months ]
• Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) ]

Original Primary Outcome Measures (submitted: September 3, 2015)

• Percentage of participants with objective response [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• Progression-free survival (PFS) [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• Percentage of participants with adverse events (AEs), serious adverse events and AEs of special interest [ Time Frame: up to 36 days after the last dose of study drug (up to approximately 7.5 years) ]
• Maximum serum concentration (Cmax) of MPDL3280A after the infusion on Day 1 of Cycle 1 [ Time Frame: Day 1 of Cycle 1 (3 weeks) ]
• Minimum serum concentration (Cmin) of MPDL3280A prior to the infusion [ Time Frame: up to approximately 7.5 years (assessed at Day 1 of Cycles 2, 3, 8, 12, 16, and every 8 cycles thereafter until study drug discontinuation visit or at least 90 days after the last dose of study drug) (each Cycle = 3 weeks) ]
• MPDL3280A serum concentration at washout [ Time Frame: 90 or more days after the last dose (up to approximately 7.5 years) ]
• Percentage of participants with anti-therapeutic antibody (ATA) [ Time Frame: up to approximately 7.5 years (assessed at Baseline, Day 1 of Cycles 1, 2, 3, 8, 12, 16, and every 8 cycles thereafter until study drug discontinuation visit or at least 90 days after the last dose of study drug) (each Cycle = 3 weeks) ]

Current Secondary Outcome Measures (submitted: February 24, 2020)

• Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months) ]
• Overall Survival (OS) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From baseline up to approximately 42 months ]
  Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
• Optimal Dose of Atezolizumab in Young Adult Participants [ Time Frame: From baseline up to approximately 42 months ]
  Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.

Original Secondary Outcome Measures (submitted: September 3, 2015)

• Duration of response (DOR) as determined by the investigator using RECIST version 1.1 [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• Overall survival (OS) [ Time Frame: Baseline until death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• PFS time as determined by investigator using immune-related response criteria (irRC) [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• Percentage of participants with ORR as determined investigator using irRC [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]
• DOR as determined investigator using irRC [ Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 7.5 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Drug: Atezolizumab

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

Other Name: RO5541267; MPDL3280A; Tecentriq

Study Arms

Experimental: Atezolizumab

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

Intervention: Drug: Atezolizumab

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 24, 2020): 87
• Original Estimated Enrollment (submitted: September 3, 2015): 100
• Actual Study Completion Date: June 6, 2019
• Actual Primary Completion Date: June 6, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Austria, Ireland

Administrative Information

• NCT Number: NCT02541604
• Other Study ID Numbers: GO29664; 2014-004697-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2020