This study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab in combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU) (FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in participants with solid tumors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
243
5-FU (400 mg/m\^2) will be administered as an IV bolus, followed by 2400 mg/m\^2 by continuous IV infusion over 46 (± 1) hours, q2w.
Participants will receive atezolizumab in a flat dose of 1200 mg q3w (Arm A, Group E2, and Arm F) or 840 mg q2w (Arm B, Arm C, and Groups E1 and E3).
Participants will receive bevacizumab at 15 mg/kg q3w (Arm A and Group F1) or 10 mg/kg q2w (Arm B).
Number of Participants With At Least One Adverse Event, with Severity Determined According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: From screening to up to 90 days after the last dose of study drug (up to approximately 55 months)
Percentage of Participants with Objective Response as Determined By The Independent Review Facility (IRF) According To Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Arm A)
Time frame: From screening to end of study (approximately 55 months)
Progression-Free Survival (PFS) as determined by the Independent Review Facility (IRF) according to RECIST v 1.1 (Arm F)
Time frame: From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)
Serum Concentrations of Atezolizumab (All Arms)
Time frame: Predose (0 hour[h]), 30 minutes(min) postdose on Day 1 of Cycles(Cy) 1 and 3; Predose(0h) on Day 1 of Cy 2,4,8 and every 8 Cy until treatment discontinuation (up to 55 months); 120 days after last dose (Cy length=21-28 days; up to 55 months)
Serum Concentrations of Bevacizumab (Arm A, Arm B and Group F1)
Time frame: Predose (0 h) and 30 min postdose (infusion length=30-90 min) on Day 1 of Cy 1 and 3; at treatment discontinuation (up to 55 months); at 120 days after last dose (Cy length=21-28 days; up to 55 months)
Plasma Concentration of Oxaliplatin (Arm B and Group E1)
Time frame: Predose (0 h) and 5-10 min before the end of infusion (infusion length=120 min) on Day 1 of Cycles 1 and 3 (Cycle length=21-28 days; up to approximately 3 months)
Plasma Concentration of 5-FU (Arm B and Arm E)
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Gemcitabine will be administered according to the local prescribing information. The starting dose-level of gemcitabine (1000 mg/m\^2) will be administered intravenously over 35 (± 5) minutes on Days 1, 8, and 15 of each 28-day cycle (3-weeks-on/1-week-off schedule).
Leucovorin 200 mg/m\^2 L-isomer form or 400 mg/m\^2 D,L-racemic form will be administered IV over 120 (± 15) minutes, q2w.
Nab-Paclitaxel will be administered according to the local prescribing information. The starting dose-level of nab-paclitaxel (125 mg/m\^2) will be administered intravenously over 35 (± 5) minutes on Days 1, 8, and 15 of each 28-day cycle (3-weeks-on/1-week-off schedule).
Oxaliplatin 85 mg/m\^2 will be administered IV over 120 (± 5) minutes q2w.
Capecitabine may be administered after 6 months at the discretion of the investigator (range of 650-1000 mg/m\^2) twice daily on Days 1-4 of a 21-day cycle.
Cisplatin will be administered as 80 mg/m\^2 IV over 120 minutes q3w (Group E2).
Stanford Cancer Institute; Hematology
Palo Alto, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Columbia University Medical Center
New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke Cancer Institute
Durham, North Carolina, United States
...and 20 more locations
Time frame: Predose (0 h), immediately following bolus administration and 2 hours post-bolus dose on Day 1 of Cycles 1 and 3 (Cycle length=21-28 days; up to approximately 3 months)
Plasma Concentration of Cisplatin (Group E2)
Time frame: Predose (0 h) and 5-10 minutes before the end of infusion (infusion length=120 min) on Day 1 of Cycles 1 and 3 (Cycle length=21 days; up to approximately 3 months)
Plasma Concentration of nab-Paclitaxel (Arm C)
Time frame: Predose (0 h), 5-10 minutes before the end of infusion and 1 hour after the end of the infusion (infusion length=35 min) on Day 1 of Cycles 1 and 3 (Cycle length=28 days; up to approximately 3 months)
Plasma Concentration of Gemcitabine (Arm C)
Time frame: Predose (0 h), 5-10 minutes before the end of infusion and 1 hour after the end of the infusion (infusion length=35 min) on Day 1 of Cycles 1 and 3 (Cycle length=28 days) (up to approximately 3 months)
Percentage of Participants with Objective Response as Determined by the IRF according to RECIST v 1.1 (Arm F)
Time frame: Baseline, every 8 weeks (± 1 week) for the first 12 months following Cycle 1 Day 1, and every 12 weeks (± 1 week) thereafter up to study completion (Cycle length=21-28 days; up to approximately 55 months)
Percentage of Participants with Objective Response as Determined By The Investigator According To RECIST v 1.1 (Arm A and Arm F)
Time frame: Baseline, every 8 weeks (± 1 week) for the first 12 months following Cycle 1 Day 1, and every 12 weeks (± 1 week) thereafter up to study completion (Cycle length=21-28 days; up to approximately 55 months)
Percentage of Participants with Objective Response as Determined by the IRF according to HCC-Specific Modified RECIST (mRECIST) (Arm A and Arm F)
Time frame: Baseline, every 8 weeks (± 1 week) for the first 12 months following Cycle 1 Day 1, and every 12 weeks (± 1 week) thereafter up to study completion (Cycle length=21-28 days; up to approximately 55 months)
Duration of Objective Response as Determined by the IRF according to RECIST v1.1 (Arm A and Arm F)
Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever comes first (up to approximately 55 months)
Duration of Objective Response as Determined by The Investigator According to RECIST v 1.1 (Arm A and Arm F)
Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever comes first (up to approximately 55 months)
Duration of Objective Response as Determined by the IRF According to HCC-Specific mRECIST (Arm A and Arm F)
Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever comes first (up to approximately 55 months)
PFS Duration as Determined by The IRF According to RECIST v1.1 (Arm A)
Time frame: From the first dose of study treatment to the first occurrence of disease progression or death from any cause, whichever comes first (up to approximately 55 months)
PFS Duration as Determined by the Investigator According To RECIST v 1.1 (Arm A and Arm F)
Time frame: From the first dose of study treatment (Arm A) or randomization (Arm F) to the first occurrence of disease progression or death from any cause, whichever comes first (up to approximately 55 months)
PFS Duration as Determined by the IRF Acording to HCC-Specific mRECIST (Arm A and Arm F)
Time frame: From the first dose of study treatment (Arm A) or randomization (Arm F) to the first occurrence of disease progression or death from any cause, whichever comes first (up to approximately 55 months)
Overall Survival (OS) Duration (Arm A and Arm F)
Time frame: Baseline up to study completion or death, whichever occurs first (up to approximately 55 months)
Time to Radiological Progression (TTRP) as Determined by the IRF According to RECIST v1.1 (Arm A and Arm F)
Time frame: From the first dose of study treatment (Arm A) or randomization (Arm F) to the first occurrence of radiographic disease progression (up to approximately 55 months)
TTRP as Determined by The Investigator According to RECIST (Arm A and Arm F)
Time frame: From the first dose of study treatment (Arm A) or randomization (Arm F) to the first occurrence of radiographic disease progression (up to approximately 55 months)
TTRP as Determined by The IRF According to HCC-Specific mRECIST (Arm A and Arm F)
Time frame: From the first dose of study treatment (Arm A) or randomization (Arm F) to the first occurrence of radiographic disease progression (up to approximately 55 months)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)
Time frame: Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 and every 8 cycles until treatment discontinuation (up to 55 months); at 120 days after last dose (Cycle length =21-28 days; up to 55 months)