Clinical trial NCT02876224: Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors
Official title: A Phase Ib Open-Label Study Evaluating the Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Bevacizumab and Immunotherapy When Administered in Patients With Gastrointestinal and Other Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-08-23
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, single-arm, two-stage, Phase Ib study designed to assess the safety, tolerability, and pharmacokinetics of oral cobimetinib with intravenous (IV) atezolizumab and bevacizumab in participants with metastatic colorectal cancer (mCRC) who have received and progressed on at least one prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan. There are two stages in this study: Stage 1 (safety run-in phase) and Stage 2 (dose expansion phase with two cohorts, an expansion cohort and a biopsy cohort).


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group performance status of 0 or 1
* Histologically confirmed unresectable metastatic colorectal adenocarcinoma
* Life expectancy at least 12 weeks
* Progression on a prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan for unresectable metastatic colorectal adenocarcinoma
* Measurable disease per RECIST v1.1
* Adequate hematologic and end organ function
* Creatinine clearance greater than or equal to (\>=) 30 milliliters per minute (mL/min)
* For biopsy cohort, participants must be bevacizumab naive or received the last bevacizumab treatment at least 12 months prior to Cycle 1 Day 1 and according to the investigator's judgment the planned biopsies would not expose participants to substantially increased risk of complications
* For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 180 days after the last study treatment
* For men, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

* More than one prior line of systemic therapy for advanced CRC
* Participants with known microsatellite (MSI)-high status
* Major surgery or significant traumatic injury within 60 days prior to enrollment
* Minor surgical procedure within 15 days of study Cycle 1 Day 1
* Untreated central nervous system (CNS) metastases
* Treatment with any investigational agent or approved therapy within 28 days
* Malignancies other than colorectal cancer within 5 years prior to Cycle 1 Day 1
* Prior radiation therapy within 30 days prior to study Cycle 1 Day 1 and/or persistence of radiation-related adverse effects
* Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past
* Spinal cord compression not definitively treated with surgery and/or radiation
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Current or recent use of therapeutic oral or parenteral anticoagulants or thrombolytic agents
* Intake of St. John's wort or hyperforin (potent cytochrome P450 \[CYP\] 3A4 enzyme inducer) or grapefruit juice (potent CYP3A4 enzyme inhibitor) within 7 days prior to initiation of study treatment
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any components of cobimetinib, atezolizumab, or bevacizumab formulations
* Prior treatment with clusters of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockage therapies, anti-programmed death protein-1, anti-program death-ligand 1, mitogen-activated protein kinase (MEK) inhibitor
* Proteinuria value \> 1.0 g at screening
* Uncontrolled glaucoma with intraocular pressure ≥ 21 mmHg
* Hyperglycemia (fasting) ≥ Grade 2
* Human Immunodeficiency Virus (HIV) infection
* Active hepatitis B or hepatitis C
* History of autoimmune disease, clinically significant cardiac or pulmonary dysfunction
* Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 or at any time during the study and for at least 5 months after the last dose of study drug
* History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
* Uncontrolled tumor pain

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 12 months
Secondary outcomes:
measure: Plasma Maximum Concentration (Cmax) of Cobimetinib
timeFrame: Safety run-in phase and expansion cohort: Predose (0 hours) on Cycle 1 Day 15 and Cycle 3 Day 15; 2 to 4 hours postdose on Cycle 1 Day 1 and Cycle 3 Day 15. Biopsy cohort: 0-2 hours predose and 2-4 hours postdose on Cycle 2 Day 1. Each cycle is 28 days.
measure: Plasma Minimum Concentration (Cmin) of Cobimetinib
timeFrame: Safety run-in phase and expansion cohort: Predose (0 hours) on Cycle 1 Day 15 and Cycle 3 Day 15; 2 to 4 hours postdose on Cycle 1 Day 1 and Cycle 3 Day 15. Biopsy cohort: 0-2 hours predose and 2-4 hours postdose on Cycle 2 Day 1. Each cycle is 28 days.
measure: Serum Cmax of Atezolizumab
timeFrame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
measure: Serum Cmin of Atezolizumab
timeFrame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
measure: Serum Cmin of Bevacizumab
timeFrame: Safety run-in phase and expansion cohort: prior to the infusion (0 hours) on Cycle 3 Day 15. Biopsy cohort: prior to the infusion (0 hours) on Cycle 3 Day 1. Each cycle is 28 days.
measure: Percentage of Participants with Anti-therapeutic Antibodies (ATAs) Response to Atezolizumab
timeFrame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: