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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atezolizumab Monotherapy: PK and Extension Phases | Experimental | Participants during the PK and extension phases of the study will receive atezolizumab alone at a dose of 1200 milligrams (mg) IV every 3 weeks (q3w) (in 21-day cycles) continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion. |
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| Atezolizumab and Chemotherapy: Extension Phase | Experimental | Participants during the extension phase of the study will receive atezolizumab at a dose of 1200 mg IV on Day 1 in combination with gemcitabine at a dose of 1250 milligrams per square meter (mg/m^2) on Days 1 and 8 and cisplatin at a dose of 75 mg/m^2 on Day 1 (four or six 21-day cycles at the discretion of the investigator), followed by atezolizumab as a single agent at a dose of 1200 mg IV q3w on Day 1 of a 21-day cycle) as maintenance treatment continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Atezolizumab | 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 | 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 | 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) | 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) | 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) | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | 100142 | China | |||
| Jilin Cancer Hospital |
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| Gemcitabine | Drug | Gemcitabine will be administered to participants with NSCLC at a dose of 1250 mg/m^2 on Days 1 and 8. |
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| Cisplatin | Drug | Cisplatin will be administered to participants with NSCLC at a dose of 75 mg/m^2 on Day 1. |
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| Terminal Half-Life (t1/2) of Atezolizumab (PK phase only) | 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) | From the first occurrence of a PR or CR through the end of study (maximum up to 3 years) |
| 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 | 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) | 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 | 6 Months; 1 Year |
| Percentage of Participants with Adverse Events (AE) | From baseline through the end of study (maximum up to 3 years) |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATA) to Atezolizumab | From first dose of atezolizumab (Day 1) through the end of study (maximum up to 3 years) |
| Changchun |
| 132013 |
| China |
| Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology | Guangzhou | 510060 | China |
| Sir Run Run Shaw Hospital | Hangzhou | 310018 | China |
| Harbin Medical University Cancer Hospital | Harbin | 150081 | China |
| Zhongshan Hospital Fudan University | Shanghai | 200032 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 200120 | China |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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