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A Phase 1 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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01375842
First received: June 16, 2011
Last updated: February 10, 2017
Last verified: February 2017

June 16, 2011
February 10, 2017
June 2011
September 2017   (Final data collection date for primary outcome measure)
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day (D) 1 up to D21 ]
  • Maximum Tolerated Dose (MTD) of Atezolizumab [ Time Frame: D1 up to D21 ]
  • Recommended Phase 2 Dose (RP2D) of Atezolizumab [ Time Frame: Baseline up to time of determination of MTD (up to D21) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 90 days after the last dose of study treatment (ST) or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately [app] 5 years [yrs]) ]
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to day 21 ]
  • Nature of dose limiting toxicities (DLTs) [ Time Frame: Up to day 21 ]
Complete list of historical versions of study NCT01375842 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Predose (prd;0hour[h]) on D1 of Cycle (Cy) 1,2,4,8,16,17,20 (1 Cy=21 days), every 8 cycles thereafter at treatment discontinuation (TD) & then every 30 days (up to 120 days) after last dose of ST/TD, death/closing of study (up to app 5 yrs) ]
  • Area Under the Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: Prd (0h),0.5h post dose on D1 of Cy 1-5,7 (1Cy=21 days);D2,4,8,15 of Cy1;prd(0h) on D1 of Cy 8,10,12,14,16,17,20, every 8 cycles thereafter & then up to every 30 days (up to 120 days) after last dose of ST/TD, death or closing of study (up to app 5 yrs) ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Prd (0h),0.5h post dose on D1 of Cy 1-5,7 (1Cy=21 days);D2,4,8,15 of Cy1;prd(0h) on D1 of Cy 8,10,12,14,16,17,20, every 8 cycles thereafter & then up to every 30 days (up to 120 days) after last dose of ST/TD, death or closing of study (up to app 5 yrs) ]
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Prd (0h) on D1 of Cy1,2,3,4,5,7,8,10,12,14,16,17,20 (1Cy=21 days), every 8 cycles upto every 30 days (up to 120 days) after last dose of ST or TD, death or closing of study (up to approximately 5 yrs) ]
  • Clearance (CL) of Atezolizumab [ Time Frame: Prd (0h),0.5h post dose on D1 of Cy 1-5,7 (1Cy=21 days);D2,4,8,15 of Cy1;prd(0h) on D1 of Cy 8,10,12,14,16,17,20, every 8 cycles thereafter & then up to every 30 days (up to 120 days) after last dose of ST/TD, death or closing of study (up to app 5 yrs) ]
  • Volume at Steady State (Vss) of Atezolizumab [ Time Frame: Prd (0h),0.5h post dose on D1 of Cy 1-5,7 (1Cy=21 days);D2,4,8,15 of Cy1;prd(0h) on D1 of Cy 8,10,12,14,16,17,20, every 8 cycles thereafter & then up to every 30 days (up to 120 days) after last dose of ST/TD, death or closing of study (up to app 5 yrs) ]
  • Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and Immune-Related Response Criteria (irRC) [ Time Frame: Baseline up to approximately 5 years (assessed every 6 weeks for 24 weeks therafter every 12 weeks until disease progression or death or initiation of further systemic cancer therapy up to app 5 years) ]
  • Percentage of Participants With Objective Response, Assessed by RECIST v1.1 and irRC [ Time Frame: Baseline, every 6 weeks for 24 weeks and every 12 weeks thereafter until disease progression, death or initiation of further systemic cancer therapy (up to approximately 5 years) ]
  • Duration of Objective Response, Assessed by RECIST v1.1 and irRC [ Time Frame: Baseline, every 6 weeks for 24 weeks and every 12 weeks thereafter until disease progression, death or initiation of further systemic cancer therapy (up to approximately 5 years) ]
  • Progression-Free Survival (PFS), Assessed by RECIST v1.1 and irRC [ Time Frame: Baseline, every 6 weeks for 24 weeks and every 12 weeks thereafter until disease progression, death or initiation of further systemic cancer therapy (up to approximately 5 years) ]
  • Incidence of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
  • Nature of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
  • Severity of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
Not Provided
Not Provided
 
A Phase 1 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
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
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 by intravenous (IV) infusion every three weeks (q3w) 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.
Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
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 0.01 mg/kg)
    Participants will receive IV infusion of atezolizumab (0.01 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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.
    Intervention: Drug: Atezolizumab
  • 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 </= exposures achieved at the MTD or maximum administered dose (MAD), will be selected for expansion cohort.
    Intervention: Drug: Atezolizumab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
698
May 2018
September 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age greater than equal to [>/=] 18 years, 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 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)
  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France,   Spain,   United Kingdom
 
 
NCT01375842
PCD4989g, 2011-001422-23, GO27831
Not Provided
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP