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
- Registration Number
- NCT01375842
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This Phase I, multicenter, first-in-human, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of atezolizumab (MPDL3280A) administered as single agent to participants with locally advanced or metastatic solid malignancies or hematologic malignancies. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 661
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation Cohort: Atezolizumab 20 mg/kg Atezolizumab 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. Expansion Cohort (Atezolizumab) 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. Dose Escalation Cohort: Atezolizumab 0.01 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 0.03 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 0.1 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 1 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 0.3 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 3 mg/kg Atezolizumab 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. Dose Escalation Cohort: Atezolizumab 10 mg/kg Atezolizumab 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.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Atezolizumab Day 1 up to Day 21 Percentage of Participants With Adverse Events 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]) Number of Participants With Dose Limiting Toxicities (DLTs) Day 1 up to Day 21 Recommended Phase 2 Dose (RP2D) of Atezolizumab Baseline up to time of determination of MTD (up to Day 21)
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) 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) Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1 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 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 from the first occurrence of a documented objective response to the time of relapse or death from any cause (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) 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) From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) Area Under the Concentration-Time Curve (AUC) of Atezolizumab 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 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 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 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 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)
Duration of Objective Response, Assessed by irRC 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 From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) PFS, Assessed by irRC From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
Trial Locations
- Locations (21)
The Angeles Clinic
🇺🇸Los Angeles, California, United States
Uni of Chicago
🇺🇸Chicago, Illinois, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Johns Hopkins Univ Med Center
🇺🇸Baltimore, Maryland, United States
HonorHealth Research Institute - Pima Center
🇺🇸Scottsdale, Arizona, United States
Stanford Univ Medical Center; Dept Central Pharmacy
🇺🇸Stanford, California, United States
Barts & London School of Med; Medical Oncology
🇬🇧London, United Kingdom
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Beth Israel Deaconess Med Ctr
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States
Dana Farber Can Ins
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada - Eastern Avenue
🇺🇸Las Vegas, Nevada, United States
Sarah Cannon Research Inst.
🇺🇸Nashville, Tennessee, United States
Centre Leon Berard
🇫🇷Lyon, France
Carolina BioOncology Institute; Can Therapy & Res Ctr
🇺🇸Huntersville, North Carolina, United States
Institut Claudius Regaud; Departement Oncologie Medicale
🇫🇷Toulouse, France
Institut Gustave Roussy; Drct
🇫🇷Villejuif, France
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States