Solid Tumor
Conditions
Brief summary
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.
Interventions
DRUGBevacizumab
Participants will receive bevacizumab at 15 mg/kg q3w (Arm A and Group F1) or 10 mg/kg q2w (Arm B).
DRUGAtezolizumab
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).
DRUG5-FU
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.
DRUGGemcitabine
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).
DRUGLeucovorin
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.
DRUGNab-Paclitaxel
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).
DRUGOxaliplatin
Oxaliplatin 85 mg/m\^2 will be administered IV over 120 (± 5) minutes q2w.
DRUGCapecitabine
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.
DRUGCisplatin
Cisplatin will be administered as 80 mg/m\^2 IV over 120 minutes q3w (Group E2).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion criteria * Measurable disease per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate hematologic and end organ function * Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade less than or equal to (\</=) 1 prior to study entry, with the exception of alopecia * Ready to use reliable contraceptive procedures Inclusion Criteria Specific to HCC (Arm A and Arm F): * Participants with advanced or metastatic and/or unresectable HCC * The participant has disease that is not amenable to a curative approach * No prior line of systemic therapy (includes participants who are sorafenib-naïve) * Willing to undergo fresh liver biopsy if provided archival tissue was taken greater than (\>) 6 months from Cycle 1 Day 1 * Child-Pugh Score of up to B7 * Serum bilirubin \</= 3 times upper limit of normal (x ULN) * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) \</= 2 x ULN * Albumin \>2.8 grams per deciliter (g/dL) * Documented virology status of hepatitis, as confirmed by screening hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or anti-hepatitis C virus (anti-HCV) * Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV) Inclusion Criteria Specific to Arm A (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm A:) * Child-Pugh score of up to B7 * Willing to undergo biopsy if archival tissue is not available or if archival tissue was taken \>6 months from Cycle 1, Day 1 * Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV). Inclusion Criteria Specific to Arm F (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm F:) * LIfe expectancy \>=3 months, as determined by the investigator * Child-Pugh score A * Platelet count ≥ 75x109/L (75,000/uL) without transfusion * Availability at the site of tumor specimens in paraffin blocks (preferred) or 16 unstained slides, with an associated pathology report, prior to study entry * Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV). Inclusion Criteria Specific to Gastric Cancer (Arm B) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm B:) * Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ in participants who have not received prior systemic therapy for metastatic disease * Absence of HER2 expression documented as in situ hybridization (ISH) negative on previously collected and assessed tumor tissue upon initial diagnosis of disease Inclusion criteria specific to metastatic pancreatic cancer (Arm C) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm C:) * Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas * No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease Inclusion Criteria Specific to mEC (Arm E) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm E:) * Histologically or cytologically confirmed locally mEC or metastatic adenocarcinoma of the GEJ Siewert Classification Type I in participants who have not received prior systemic therapy for primary and metastatic disease or chemoradiation therapy for primary disease * Absence of HER2 expression documented as ISH-negative on previously collected and assessed tumor tissue upon initial diagnosis of disease * Willing to undergo biopsy if archival tissue is not available or if archival tissue was taken \>6 months from Cycle 1 Day 1
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) | 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) | 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) | From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Concentration of 5-FU (Arm B and Arm E) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) |
| Serum Concentrations of Atezolizumab (All Arms) | 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) |
| PFS Duration as Determined by The IRF According to RECIST v1.1 (Arm A) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) |
| Duration of Objective Response as Determined by the IRF According to HCC-Specific mRECIST (Arm A and Arm F) | 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) |
| Serum Concentrations of Bevacizumab (Arm A, Arm B and Group F1) | 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) | 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) |
Countries
Australia, China, Japan, New Zealand, South Korea, Taiwan, United States
Outcome results
None listed