A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PDL1] Antibody) to Evaluate Safety, Tolerability and Pharmacokinetics in Participants With Locally Advanced or Metastatic Solid Tumors
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ClinicalTrials.gov Identifier: NCT01375842 |
Recruitment Status :
Completed
First Posted : June 17, 2011
Last Update Posted : December 11, 2018
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Condition or disease | Intervention/treatment | Phase |
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Tumors Hematologic Malignancies | Drug: Atezolizumab | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 661 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) Administered Intravenously as a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies |
Actual Study Start Date : | June 21, 2011 |
Actual Primary Completion Date : | September 30, 2018 |
Actual Study Completion Date : | September 30, 2018 |
Arm | Intervention/treatment |
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Experimental: Dose Escalation Cohort: Atezolizumab 0.01 mg/kg
Participants will receive intravenous (IV) infusion of atezolizumab 0.01 milligrams per kilogram (mg/kg) every 3 weeks (q3w) until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
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Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 0.03 mg/kg
Participants will receive IV infusion of atezolizumab 0.03 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
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Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 0.1 mg/kg
Participants will receive IV infusion of atezolizumab 0.1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 0.3 mg/kg
Participants will receive IV infusion of atezolizumab 0.3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 1 mg/kg
Participants will receive IV infusion of atezolizumab 1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 3 mg/kg
Participants will receive IV infusion of atezolizumab 3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 10 mg/kg
Participants will receive IV infusion of atezolizumab 10 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Dose Escalation Cohort: Atezolizumab 20 mg/kg
Participants will receive IV infusion of atezolizumab 20 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
Experimental: Expansion Cohort (Atezolizumab)
Participants will receive IV infusion of atezolizumab q3w up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. The dose which result in total drug exposure less than or equal to (</=) exposures achieved at the MTD or maximum administered dose (MAD), will be selected for expansion cohort.
|
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A |
- Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 up to Day 21 ]
- Maximum Tolerated Dose (MTD) of Atezolizumab [ Time Frame: Day 1 up to Day 21 ]
- Recommended Phase 2 Dose (RP2D) of Atezolizumab [ Time Frame: Baseline up to time of determination of MTD (up to Day 21) ]
- Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 90 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately [approx] 7 years [yrs]) ]
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Predose(0 hour[hr])on Day 1 of Cycles 1,2,4,8,16,17,20(Cycle length=21 days), every 8 cycles thereafter, at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure(up to approx 7 yrs) ]
- Area Under the Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohort: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
- Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
- Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
- Clearance (CL) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
- Volume at Steady State (Vss) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
- Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
- Percentage of Participants With Best Overall Response, Assessed by Immune-Related Response Criteria (irRC) [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
- Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1 [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
- Percentage of Participants With Objective Response (CR or PR), Assessed by irRC [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
- Duration of Objective Response, Assessed by RECIST v1.1 [ Time Frame: Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) ]
- Duration of Objective Response, Assessed by irRC [ Time Frame: Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) ]
- Progression-Free Survival (PFS), Assessed by RECIST v1.1 [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
- PFS, Assessed by irRC [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor
- Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
- Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report
- Adequate hematologic and end organ function
- Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- For participants who will undergo serial biopsy in dose-escalation cohort, baseline tumor tissue samples should be of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions (>/=5 millimeter [mm] in diameter amenable to serial biopsy)
Exclusion Criteria:
- Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
- Known hypersensitivity to pharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History or risk of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis)
- History of human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection
- Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1
- Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01375842
Study Director: | Clinical Trials | Genentech, Inc. |
Responsible Party: | Genentech, Inc. |
ClinicalTrials.gov Identifier: | NCT01375842 |
Other Study ID Numbers: |
PCD4989g 2011-001422-23 ( EudraCT Number ) GO27831 ( Other Identifier: Hoffmann-La Roche ) |
First Posted: | June 17, 2011 Key Record Dates |
Last Update Posted: | December 11, 2018 |
Last Verified: | December 2018 |
Neoplasms Hematologic Neoplasms Neoplasms by Site Hematologic Diseases Atezolizumab |
Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |