Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

• Status: Completed
• Trial end date: 2019-11-04
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Antibodies, Monoclonal; Atezolizumab

Criteria

Inclusion Criteria:

• Solid tumor that is metastatic, locally advanced or recurrent

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy greater than or equal to (>/=) 12 weeks

• Measurable disease, as defined by RECIST v 1.1

• Adequate hematologic and end organ function

• Use of highly effective contraception

• Histological tumor tissue specimen

• Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:

• Metatastic colorectal cancer

• Non-small cell lung cancer

• Melanoma

Exclusion Criteria:

Cancer-Specific Exclusion Criteria:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment

• Known active or untreated central nervous system (CNS) metastases

• Leptomeningeal disease

• Uncontrolled tumor-related pain or uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent (once monthly or more frequently) drainage procedures

• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab

General Medical Exclusion Criteria:

• Pregnant and lactating women

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cell or any component of the atezolizumab formulation

• History of autoimmune disease

• Participants with prior allogeneic stem cell or solid organ transplantation

• Positive test for human immunodeficiency virus (HIV)

• Participants with active hepatitis B, hepatitis C, or tuberculosis

• Severe infections within 4 weeks prior to Cycle 1 Day 1

• Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1

• Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1

• Significant cardiovascular disease

• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day 1 or anticipation of need for a major surgical procedure during the course of the study

• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

Exclusion Criteria Unique to Cobimetinib:

• History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment

• Allergy or hypersensitivity to components of the cobimetinib formulations

• History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds at screening

• Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or Multi Gated Acquisition Scan (MUGA) scan

• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration

• History of malabsorption syndrome or other condition that would interfere with enteral absorption

Exclusion Criteria Related to Medications:

• Prior treatment with clusters of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, systemic immunostimulatory agents, or systemic immunosuppressive medications