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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: April 4, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
Drug: Atezolizumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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]) ]

Secondary Outcome Measures:
  • 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) ]

Enrollment: 698
Actual Study Start Date: June 30, 2011
Estimated Study Completion Date: May 31, 2018
Estimated Primary Completion Date: September 30, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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 </= 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01375842

  Show 21 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01375842     History of Changes
Other Study ID Numbers: PCD4989g
2011-001422-23 ( EudraCT Number )
GO27831 ( Other Identifier: Hoffmann-La Roche )
Study First Received: June 16, 2011
Last Updated: April 4, 2017

Keywords provided by Genentech, Inc.:
PD-L1
PD-1
lymphoma
esophageal cancer
antiPD-L1
MPDL3280A
Solid tumor
Renal cell Carcinoma (RCC)
Melanoma (MEL)
Non-small Cell Lung Cancer (NSCLC)
Breast Cancer
Gastric Cancer
Head and Neck Cancer
Colorectal Cancer
Heme Malignancies
Non-Hodgkin Lymphoma
Multiple Myeloma
MPDL320A

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2017