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

NCT01375842 | Completed Phase 1

• 3 other identifiers: PCD4989g2011-001422-23GO27831
• Study Type: interventional
• Target: 661
• Locations: 4 countries
• Sites: 21

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.

Conditions

Tumors; Hematologic Malignancies

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  Day 1 up to Day 21

• Maximum Tolerated Dose (MTD) of Atezolizumab

  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)

• 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 Outcomes (14)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (9)

Dose Escalation Cohort: Atezolizumab 0.01 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 0.03 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 0.1 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 0.3 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 1 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 3 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 10 mg/kg

EXPERIMENTAL

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

Dose Escalation Cohort: Atezolizumab 20 mg/kg

EXPERIMENTAL

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

Expansion Cohort (Atezolizumab)

EXPERIMENTAL

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

Interventions

Atezolizumab DRUG

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.

Also known as: MPDL3280A

Dose Escalation Cohort: Atezolizumab 0.01 mg/kg; Dose Escalation Cohort: Atezolizumab 0.03 mg/kg; Dose Escalation Cohort: Atezolizumab 0.1 mg/kg; Dose Escalation Cohort: Atezolizumab 0.3 mg/kg; Dose Escalation Cohort: Atezolizumab 1 mg/kg; Dose Escalation Cohort: Atezolizumab 10 mg/kg; Dose Escalation Cohort: Atezolizumab 20 mg/kg; Dose Escalation Cohort: Atezolizumab 3 mg/kg; Expansion Cohort (Atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (21)

HonorHealth Research Institute - Pima Center

Scottsdale, Arizona, 85258, United States

Location

The Angeles Clinic

Los Angeles, California, 90025, United States

Location

Stanford Univ Medical Center; Dept Central Pharmacy

Stanford, California, 94305, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33647, United States

Location

Uni of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Univ Med Center

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, 89169, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

Carolina BioOncology Institute; Can Therapy & Res Ctr

Huntersville, North Carolina, 28078, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy; Drct

Villejuif, 94805, France

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Barts & London School of Med; Medical Oncology

London, EC1A 7BE, United Kingdom

Location

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MeSH Terms

Conditions

Neoplasms; Hematologic Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 17, 2011
• Study Start: June 21, 2011
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: December 11, 2018

Record last verified: 2018-12

Locations

FR (3); ES (1); US (16); GB (1)