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

Hematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01375842
• Other study ID #: PCD4989g
• Secondary ID: 2011-001422-23GO
• Status: Completed
• Phase: Phase 1
• Start date: June 21, 2011
• Est. completion date: September 30, 2018

Study information

• Verified date: December 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 661
• Est. completion date: September 30, 2018
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancies
• Neoplasms
• Tumors

Intervention

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.

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Institut Gustave Roussy; Drct	Villejuif
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United Kingdom	Barts & London School of Med; Medical Oncology	London
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Johns Hopkins Univ Med Center	Baltimore	Maryland
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Dana Farber Can Ins	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Uni of Chicago	Chicago	Illinois
United States	Carolina BioOncology Institute; Can Therapy & Res Ctr	Huntersville	North Carolina
United States	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada
United States	The Angeles Clinic	Los Angeles	California
United States	Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Vanderbilt	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	HonorHealth Research Institute - Pima Center	Scottsdale	Arizona
United States	Stanford Univ Medical Center; Dept Central Pharmacy	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLTs)		Day 1 up to Day 21
Primary	Maximum Tolerated Dose (MTD) of Atezolizumab		Day 1 up to Day 21
Primary	Recommended Phase 2 Dose (RP2D) of Atezolizumab		Baseline up to time of determination of MTD (up to Day 21)
Primary	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	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)
Secondary	Area Under the Concentration-Time Curve (AUC) of Atezolizumab	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)	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)
Secondary	Maximum Serum Concentration (Cmax) of Atezolizumab	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)	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)
Secondary	Minimum Serum Concentration (Cmin) of Atezolizumab	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)	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)
Secondary	Clearance (CL) of Atezolizumab	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)	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)
Secondary	Volume at Steady State (Vss) of Atezolizumab	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)	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	PFS, Assessed by irRC		From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)