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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Atezolizumab 840 mg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.
Bevacizumab 5 mg/kg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.
Cobimetinib 60 mg or at dose determined during safety run-in phase will be administered orally once daily for 21 days of each 28-day cycle as specified in the arm descriptions.
University Of Colorado
Aurora, Colorado, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Sarah Cannon Research Inst.
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Hospital Universitario Vall d'Hebron
Barcelona, Spain
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, Spain
Percentage of Participants with Adverse Events
Time frame: Baseline up to approximately 12 months
Plasma Maximum Concentration (Cmax) of Cobimetinib
Time frame: 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.
Plasma Minimum Concentration (Cmin) of Cobimetinib
Time frame: 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.
Serum Cmax of Atezolizumab
Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycles 1, 2, 4, 8, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 1 Day 1 and Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.
Time frame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
Serum Cmin of Atezolizumab
Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycles 1, 2, 4, 8, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 1 Day 1 and Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.
Time frame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
Serum Cmin of Bevacizumab
Time frame: 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.
Percentage of Participants with Anti-therapeutic Antibodies (ATAs) Response to Atezolizumab
Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycle 1, 2, 4, 8, and every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.
Time frame: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)
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