This open-label, Phase Ib study that has six treatment arms is designed to assess the safety, pharmacology and preliminary efficacy of atezolizumab (MPDL3280A; an engineered anti-programmed death-ligand 1 \[PDL1\] antibody) administered with bevacizumab (Arm A) and with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (FOLFOX) (Arm B), with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with carboplatin and nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in participants with locally advanced or metastatic solid tumors. The study includes dose escalation cohort for establishing the maximum tolerated dose (MTD) or maximum administered dose (MAD) and then expansion cohort will be initiated based on a selected dose level at or below the MTD or MAD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
240
Participants will receive 5-FU 400 mg/m\^2 IV q2w.
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Participants will receive bevacizumab 10 mg/kg or 15 mg/kg IV q3w.
Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
Participants will receive leucovorin 400 mg/m\^2 IV q2w.
Participants will receive nab-paclitaxel 100 mg/m\^2 IV qw.
Participants will receive oxaliplatin 85 mg/m\^2 IV q2w.
Participants will receive paclitaxel 200 mg/m\^2 IV q3w.
Participants will receive pemetrexed 500 mg/m\^2 IV q3w.
University of Colorado Cancer Center
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Georgetown University Medical Center Lombardi Cancer Center
Washington D.C., District of Columbia, United States
Uni of Chicago
Chicago, Illinois, United States
Massachusetts General Hospital.
Boston, Massachusetts, United States
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States
Dana Farber Can Ins
Boston, Massachusetts, United States
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Carolina BioOncology Institute; Can Therapy & Res Ctr
Huntersville, North Carolina, United States
...and 1 more locations
Maximum Tolerated Atezolizumab Dose
Time frame: Days 1-21 of Cycle 1 (Cycle length = 21 days) for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B
Percentage of Participants With Adverse Events
Time frame: From Baseline up to 90 days after last dose of study drug or until initiation of another anti-cancer therapy (up to approximately 5 years)
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Days 1-21 of Cycle 1 (Cycle length = 21 days) for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B
Duration of Objective Response According to RECIST v1.1
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Duration of Objective Response According to irRC
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Progression-Free Survival According to RECIST v1.1
Time frame: From treatment initiation until documented disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Progression-Free Survival According to irRC
Time frame: From treatment initiation until documented disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of Atezolizumab
Time frame: Pre-infusion (0 hour [hr]) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Pharmacokinetics: Maximum Serum Concentration (Cmax) of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Minimum Serum Concentration (Cmin) of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Percentage of Participants With Best Overall Response According to Immune-Related Response Criteria (irRC)
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Percentage of Participants With Objective Response (Complete Response + Partial Response) According to RECIST v1.1
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Percentage of Participants With Objective Response (Complete Response + Partial Response) According to irRC
Time frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)
Pharmacokinetics: Clearance of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Pharmacokinetics: Volume of Distribution of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Pharmacokinetics: Accumulation Ratio of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Pharmacokinetics: Half-Life of Atezolizumab
Time frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)
Pharmacokinetics: Cmax of Bevacizumab
Time frame: Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years)
Pharmacokinetics: Cmin of Bevacizumab
Time frame: Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years)
Maximum Plasma Concentration of 5-FU
Time frame: Pre- infusion (0 hr) on Day 1 Cycle 1; end of 5-FU bolus and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days)
Pharmacokinetics: Maximum Plasma Concentration of Oxaliplatin
Time frame: Pre-infusion (0 hr) on Day 1 Cycle 1; 5-10 min before end of oxaliplatin infusion (infusion duration = 120 min) and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days)
Pharmacokinetics: Maximum Plasma Concentration of Carboplatin
Time frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after carboplatin EOI (infusion duration=15-30 min),24 hr after atezolizumab EOI (infusion duration=90 min)on Day 1 Cycle 1; 5-10 min before and 1 hr after carboplatin EOI Day 1 Cycle 3 (each cycle=21 days)
Maximum Plasma Concentration of Paclitaxel
Time frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after paclitaxel EOI (infusion duration=180 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after paclitaxel EOI on Day 1 Cycle 3 (each cycle=21 days)
Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed
Time frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after pemetrexed EOI (infusion duration=10 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after pemetrexed EOI on Day 1 Cycle 3 (each cycle = 21 days)
Maximum Plasma Concentration of Nab-Paclitaxel (Total Paclitaxel)
Time frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after nab-paclitaxel EOI (infusion duration=30 min) on Day 1 of Cycles 1 and 3; 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1 (each cycle=7 days)
Number of Cycles of Each Component of Treatment Administer
Time frame: From Baseline up to approximately 5 years
Dose Intensity of Each Component of Treatment Administer
Time frame: From Baseline up to approximately 5 years
Overall Survival (OS)
Time frame: From first dose of study treatment until death from any cause (up to approximately 5 years)
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