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
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Solid Tumor
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 87
- Locations
- 30
- Primary Endpoint
- Minimum Serum Concentration (Cmin) of Atezolizumab
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
Arms & Interventions
Atezolizumab
Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams \[mg\]) on Day 1 of each 21-day cycle.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
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)
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)
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.
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)
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)
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)
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 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)
Secondary Outcomes
- 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)
- 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)
- 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))