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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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01375842
Collaborator
(none)
661
Enrollment
21
Locations
9
Arms
87.3
Actual Duration (Months)
31.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
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 :
Jun 21, 2011
Actual Primary Completion Date :
Sep 30, 2018
Actual Study Completion Date :
Sep 30, 2018

Arms and Interventions

Arm Intervention/Treatment
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.

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MPDL3280A

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose Limiting Toxicities (DLTs) [Day 1 up to Day 21]

    2. Maximum Tolerated Dose (MTD) of Atezolizumab [Day 1 up to Day 21]

    3. Recommended Phase 2 Dose (RP2D) of Atezolizumab [Baseline up to time of determination of MTD (up to Day 21)]

    4. 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])]

    Secondary Outcome Measures

    1. 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)]

    2. 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)

    3. 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)

    4. 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)

    5. 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)

    6. 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)

    7. 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)]

    8. 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)]

    9. 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)]

    10. 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)]

    11. 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)]

    12. 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)]

    13. 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)]

    14. PFS, Assessed by irRC [From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Research Institute - Pima Center Scottsdale Arizona United States 85258
    2 The Angeles Clinic Los Angeles California United States 90025
    3 Stanford Univ Medical Center; Dept Central Pharmacy Stanford California United States 94305
    4 Yale Cancer Center New Haven Connecticut United States 06520
    5 Moffitt Cancer Center Tampa Florida United States 33647
    6 Uni of Chicago Chicago Illinois United States 60637
    7 Johns Hopkins Univ Med Center Baltimore Maryland United States 21231
    8 Massachusetts General Hospital. Boston Massachusetts United States 02114
    9 Beth Israel Deaconess Med Ctr Boston Massachusetts United States 02215
    10 Dana Farber Can Ins Boston Massachusetts United States 02215
    11 Comprehensive Cancer Centers of Nevada - Eastern Avenue Las Vegas Nevada United States 89169
    12 New York Oncology Hematology, P.C. Albany New York United States 12206
    13 Carolina BioOncology Institute; Can Therapy & Res Ctr Huntersville North Carolina United States 28078
    14 Sarah Cannon Research Inst. Nashville Tennessee United States 37203
    15 Vanderbilt Nashville Tennessee United States 37232
    16 Virginia Oncology Associates Norfolk Virginia United States 23502
    17 Centre Leon Berard Lyon France 69008
    18 Institut Claudius Regaud; Departement Oncologie Medicale Toulouse France 31059
    19 Institut Gustave Roussy; Drct Villejuif France 94805
    20 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    21 Barts & London School of Med; Medical Oncology London United Kingdom EC1A 7BE

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT01375842
    Other Study ID Numbers:
    • PCD4989g
    • 2011-001422-23
    • GO27831
    First Posted:
    Jun 17, 2011
    Last Update Posted:
    Dec 11, 2018
    Last Verified:
    Dec 1, 2018
    Additional relevant MeSH terms:
    Neoplasms
    Hematologic Neoplasms
    Atezolizumab

    Study Results

    No Results Posted as of Dec 11, 2018