Solid Tumor
Conditions
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.
Interventions
DRUGAtezolizumab
Atezolizumab was administered as IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Optimal Dose of Atezolizumab in Young Adult Participants | From baseline up to approximately 42 months | Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks. |
| 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) | — |
| 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) | — |
| 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) | — |
| 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) | — |
| 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) | — |
| 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 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 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) | — |
| Optimal Dose of Atezolizumab in Pediatric Adult Participants | From baseline up to approximately 42 months | Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks. |
Countries
Canada, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COHORT 1 EWING SARCOMA | 11 |
| COHORT 2 HODGKIN LYMPHOMA | 9 |
| COHORT 3 NEUROBLASTOMA | 11 |
| COHORT 4 NON HODGKIN LYMPHOMA | 3 |
| COHORT 5 NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA; | 10 |
| COHORT 6 OSTEOSARCOMA | 10 |
| COHORT 7 RHABDOMYOSARCOMA | 10 |
| COHORT 8 WILMS TUMOR | 10 |
| COHORT 9 OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION | 4 |
| COHORT 10 OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION | 4 |
| COHORT 11 RHABDOID TUMOR | 2 |
| COHORT 12 ATYPICAL TERATOID RHABDOID TUMOR | 3 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 5 | 7 | 2 | 9 | 8 | 9 | 9 | 3 | 4 | 2 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Medical condition may jeopardize safety | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 1 | 4 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | COHORT 1 | COHORT 2 | COHORT 3 | COHORT 4 | COHORT 5 | COHORT 6 | COHORT 7 | COHORT 8 | COHORT 9 | COHORT 10 | COHORT 11 | COHORT 12 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 13.6 Years STANDARD_DEVIATION 3.3 | 14.2 Years STANDARD_DEVIATION 3 | 12.8 Years STANDARD_DEVIATION 9.4 | 19.0 Years STANDARD_DEVIATION 6.6 | 14.5 Years STANDARD_DEVIATION 6.5 | 17.1 Years STANDARD_DEVIATION 4.1 | 13.0 Years STANDARD_DEVIATION 8.5 | 12.6 Years STANDARD_DEVIATION 6.8 | 14.8 Years STANDARD_DEVIATION 1 | 11.3 Years STANDARD_DEVIATION 0.5 | 0.5 Years STANDARD_DEVIATION 0.7 | 7.3 Years STANDARD_DEVIATION 4.6 | 13.5 Years STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 7 Participants | 2 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 4 Participants | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 26 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 5 Participants | 2 Participants | 6 Participants | 6 Participants | 8 Participants | 5 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 50 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 4 Participants | 0 Participants | 5 Participants | 4 Participants | 4 Participants | 6 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 40 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 7 Participants | 3 Participants | 5 Participants | 6 Participants | 6 Participants | 4 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 11 | 5 / 9 | 7 / 11 | 2 / 3 | 9 / 10 | 8 / 10 | 9 / 10 | 9 / 10 | 3 / 4 | 4 / 4 | 2 / 2 | 3 / 3 |
| other Total, other adverse events | 11 / 11 | 8 / 9 | 11 / 11 | 3 / 3 | 10 / 10 | 10 / 10 | 10 / 10 | 10 / 10 | 4 / 4 | 3 / 4 | 2 / 2 | 2 / 3 |
| serious Total, serious adverse events | 4 / 11 | 3 / 9 | 2 / 11 | 0 / 3 | 3 / 10 | 6 / 10 | 3 / 10 | 5 / 10 | 2 / 4 | 3 / 4 | 1 / 2 | 1 / 3 |
Outcome results
Primary
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)
Population: Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Area Under the Concentration-Time Curve (AUC) of Atezolizumab | 1130 ugxday/mL | Geometric Coefficient of Variation 5.28 |
| Cohort 5 | Area Under the Concentration-Time Curve (AUC) of Atezolizumab | 2209 ugxday/mL | Geometric Coefficient of Variation 21.3 |
| Cohort 6 | Area Under the Concentration-Time Curve (AUC) of Atezolizumab | 2816 ugxday/mL | Geometric Coefficient of Variation 17.7 |
| Cohort 7 | Area Under the Concentration-Time Curve (AUC) of Atezolizumab | 3579 ugxday/mL | Geometric Coefficient of Variation 28.4 |
Primary
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)
Population: Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Atezolizumab Serum Concentration at Washout | 1.91 ug/mL | Geometric Coefficient of Variation 2815.1 |
Primary
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)
Population: Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff. In the \<2 Age (Years) Arm/Group, 1 participant died after study entry with 1 cycle, and the other participant died after two cycles.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 1 | 105 ug/mL | Geometric Coefficient of Variation 6.9 |
| Cohort 5 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 1 | 312 ug/mL | Geometric Coefficient of Variation 28.7 |
| Cohort 5 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 4 | 382 ug/mL | Geometric Coefficient of Variation 16.4 |
| Cohort 6 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 4 | 373 ug/mL | Geometric Coefficient of Variation 78.9 |
| Cohort 6 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 1 | 337 ug/mL | Geometric Coefficient of Variation 26.8 |
| Cohort 7 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 1 | 424 ug/mL | Geometric Coefficient of Variation 26.9 |
| Cohort 7 | Maximum Serum Concentration (Cmax) of Atezolizumab | Cycle 4 | 626 ug/mL | Geometric Coefficient of Variation 29.2 |
Primary
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)
Population: Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff. In the \<2 Age (Years) Arm/Group, 1 participant died after study entry with 1 cycle, and the other participant died after two cycles.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 | 24.1 ug/mL | — |
| Cohort 5 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 8 | 166 ug/mL | Geometric Coefficient of Variation 19.8 |
| Cohort 5 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 | 59.3 ug/mL | Geometric Coefficient of Variation 31.4 |
| Cohort 5 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 3 | 58.9 ug/mL | Geometric Coefficient of Variation 234.4 |
| Cohort 5 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 | 99.2 ug/mL | Geometric Coefficient of Variation 36.4 |
| Cohort 6 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 3 | 85.0 ug/mL | Geometric Coefficient of Variation 47.4 |
| Cohort 6 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 | 56.5 ug/mL | Geometric Coefficient of Variation 50.4 |
| Cohort 6 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 8 | 145 ug/mL | Geometric Coefficient of Variation 21.9 |
| Cohort 6 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 | 113 ug/mL | Geometric Coefficient of Variation 41.1 |
| Cohort 7 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 8 | 209 ug/mL | Geometric Coefficient of Variation 8.1 |
| Cohort 7 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 | 79.9 ug/mL | Geometric Coefficient of Variation 52.7 |
| Cohort 7 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 3 | 148 ug/mL | Geometric Coefficient of Variation 48.9 |
| Cohort 7 | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 | 121 ug/mL | Geometric Coefficient of Variation 80.4 |
Primary
Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
Time frame: From baseline up to approximately 42 months
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest | Adverse Events | 97.7 Percentage |
| Cohort 1 | Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest | Serious Adverse Events | 37.9 Percentage |
| Cohort 1 | Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest | Adverse Events of Special Interest | 44.8 Percentage |
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.
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 0 Percentage |
| Cohort 5 | 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 | 10.0 Percentage |
| Cohort 6 | 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 | 0 Percentage |
| Cohort 7 | 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 | 0 Percentage |
| Cohort 8 | 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 | 0 Percentage |
| Cohort 9 | 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 | 0 Percentage |
| Cohort 10 | 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 | 0 Percentage |
| Cohort 11 | 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 | 0 Percentage |
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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 0 Percentage |
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)
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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) | 0 Percentage |
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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 22.2 Percentage |
| Cohort 5 | 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 | 33.3 Percentage |
Primary
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)
Population: The baseline ADA-evaluable population included patients who had a baseline ADA result. The post-baseline ADA-evaluable population included patients who had at least one post-baseline ADA result and had received at least one dose of that study treatment. Patients never dosed and patients without valid ADA records were not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Baseline | 2.6 Percentage |
| Cohort 1 | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Post-baseline | 14.3 Percentage |
Primary
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)
Population: Included safety-evaluable population (defined as patients who received any amount of study drug), in the Osteosarcoma cohort as per protocol. (Objective response for the other cohorts are measured with different response criteria, and these are described in Outcome Measures 1, 2, 3, and 4).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma | 0 Percentage |
Primary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma | 2.6 Months |
Primary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT | 1.4 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
Time frame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | 2.8 Months |
| Cohort 5 | PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | 1.4 Months |
Primary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.2 Months |
| Cohort 5 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.3 Months |
| Cohort 6 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.2 Months |
| Cohort 7 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.1 Months |
| Cohort 8 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.3 Months |
| Cohort 9 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.2 Months |
| Cohort 10 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 1.2 Months |
| Cohort 11 | Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors | 0.7 Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 5 | DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 13.2 Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | NA Months |
| Cohort 5 | DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | NA Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug. No participants had response therefore no participants analyzed.
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug. No participants had an objective response in this cohort.
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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | NA Months |
| Cohort 5 | DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | NA Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 5 | Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors | 13.2 Months |
Secondary
Optimal Dose of Atezolizumab in Pediatric Adult Participants
Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
Time frame: From baseline up to approximately 42 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Optimal Dose of Atezolizumab in Pediatric Adult Participants | 15 mg/kg |
Secondary
Optimal Dose of Atezolizumab in Young Adult Participants
Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
Time frame: From baseline up to approximately 42 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Optimal Dose of Atezolizumab in Young Adult Participants | 1200 mg |
Secondary
Overall Survival (OS)
Time frame: Baseline until death (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Overall Survival (OS) | 7.4 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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 0 Percentage |
| Cohort 5 | 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 | 10 Percentage |
| Cohort 6 | 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 | 0 Percentage |
| Cohort 7 | 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 | 0 Percentage |
| Cohort 8 | 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 | 0 Percentage |
| Cohort 9 | 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 | 0 Percentage |
| Cohort 10 | 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 | 0 Percentage |
| Cohort 11 | 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 | 0 Percentage |
| Cohort 12 | 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 | 0 Percentage |
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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 0 Percentage |
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
Time frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | 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 | 33.3 Percentage |
| Cohort 5 | 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 | 33.3 Percentage |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.3 Months |
| Cohort 5 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.4 Months |
| Cohort 6 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.2 Months |
| Cohort 7 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.3 Months |
| Cohort 8 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.4 Months |
| Cohort 9 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.2 Months |
| Cohort 10 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 1.2 Months |
| Cohort 11 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 0.7 Months |
| Cohort 12 | PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors | 6.9 Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | 6.5 Months |
| Cohort 5 | PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma | 3.7 Months |
Secondary
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)
Population: Included safety-evaluable population, defined as patients who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma | 6.9 Months |