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

Genentech

Status and phase: Completed; Phase 1

Conditions: Tumors; Hematologic Malignancies

Treatments: Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01375842

2011-001422-23 (EudraCT Number)

PCD4989g

GO27831 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 661 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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661 participants in 9 patient groups

Dose Escalation Cohort: Atezolizumab 0.01 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 0.03 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 0.1 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 0.3 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 1 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 3 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 10 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Dose Escalation Cohort: Atezolizumab 20 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Expansion Cohort (Atezolizumab)

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab