This Phase I, open-label, multicenter study will evaluate the pharmacokinetics, safety, and preliminary anti-tumor activity of atezolizumab as monotherapy in Chinese participants with locally advanced or metastatic gastric cancer, nasopharyngeal cancer, esophageal cancer, and hepatocellular carcinoma (HCC) that are refractory to standard therapeutic modalities and for whom no further standard therapy is available or who have refused standard therapy; and the safety and preliminary anti-tumor activity of atezolizumab in combination with gemcitabine and cisplatin in Chinese participants with Stage IV, treatment-naive non-small cell lung cancer (NSCLC). The study will consist of a pharmacokinetic (PK) phase and an extension phase.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Atezolizumab will be administered at a dose of 1200 mg IV q3w (in 21-day cycles), except for participants with NSCLC who will be administered atezolizumab at a dose of 1200 mg IV on Day 1.
Gemcitabine will be administered to participants with NSCLC at a dose of 1250 mg/m\^2 on Days 1 and 8.
Cisplatin will be administered to participants with NSCLC at a dose of 75 mg/m\^2 on Day 1.
Beijing Cancer Hospital
Beijing, China
Jilin Cancer Hospital
Changchun, China
Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology
Guangzhou, China
Sir Run Run Shaw Hospital
Hangzhou, China
Harbin Medical University Cancer Hospital
Harbin, China
Zhongshan Hospital Fudan University
Shanghai, China
Fudan University Shanghai Cancer Center
Shanghai, China
Maximum Observed Plasma Concentration (Cmax) of Atezolizumab
Time frame: Pre-dose (0 hours [h]), 0.5h post-dose (PtD) at Day (D) 1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Minimum Observed Plasma Concentration (Cmin) of Atezolizumab
Time frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Accumulation Ratio (R) of Atezolizumab Based on Concentrations After the First Dose and at Steady State
Time frame: Pre-dose (0h), 0.5h PtD at D 1; D2, 4, 8, 15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Area Under the Plasma Concentration-Time Curve (AUC) of Atezolizumab (PK phase only)
Time frame: Pre-dose (0h), 0.5h PtD at D 1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Systemic Clearance (CL) of Atezolizumab (PK phase only)
Time frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Volume of Distribution at Steady State (Vss) of Atezolizumab (PK phase only)
Time frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Terminal Half-Life (t1/2) of Atezolizumab (PK phase only)
Time frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 3 years)
Objective Response (OR), Defined as a Complete Response (CR) or Partial Response (PR) on Two Consecutive Occasions >/= 4 Weeks Apart, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: From the first occurrence of a PR or CR through the end of study (maximum up to 3 years)
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Time frame: From the first occurrence of a documented OR to the first occurrence of disease progression, whichever occurs first (maximum up to 3 years)
Time to Progression (TTP) (HCC Cohort) as Determined by the Investigator According to RECIST v1.1
Time frame: From the first dose of atezolizumab (Day 1) to the first occurrence of disease progression (maximum up to 3 years)
Progression-free Survival (PFS) as Determined by the Investigator According to RECIST v1.1
Time frame: From the first dose of atezolizumab (Day 1) to the first occurrence of disease progression or death, whichever comes first (maximum up to 3 years)
Overall survival (OS)
Time frame: From the first dose of atezolizumab (Day 1) to death from any cause (maximum up to 3 years)
OS at 6 Months and 1 Year
Time frame: 6 Months; 1 Year
Percentage of Participants with Adverse Events (AE)
Time frame: From baseline through the end of study (maximum up to 3 years)
Percentage of Participants with Anti-Therapeutic Antibodies (ATA) to Atezolizumab
Time frame: From first dose of atezolizumab (Day 1) through the end of study (maximum up to 3 years)
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