Patients with histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressed following at least one line of prior systemic anticancer therapy, or for which there is no alternative therapy known to prolong survival. MedDRA version: 20.0 Level: PT Classification code 10062042 Term: Lung neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10
Conditions
Interventions
Product Name: Atezolizumab
Product Code: RO5541267-F03-01
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Atezolizumab
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female, 18 years of age or older - Histologically documented advanced (i.e. stages III or IV) solid tumors that meet protocol-defined cohort specifications, with progressive disease at study entry and at least one prior line of systemic anticancer therapy or for which there is no alternative therapy known to prolong survival. - Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks or, in exceptional cases, 15 freshly cut and unstained slides, with an associated pathology report, for central testing - Measurable disease as defined by RECIST v1.1. or disease-specific criteria for prostate cancer and malignant pleural mesothelioma - Eastern Cooperative Oncology group (ECOG) Performance Status of 0 or 1 - Adequate hematologic and end organ function - Negative serum pregnancy test result within 14 days prior to initiation of study drug among women of child-bearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 545 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: - Malignancies other than disease under study within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death - Uncontrolled tumor-related pain - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab - History of treated asymptomatic or symptomatic CNS metastasis or presence of CNS metastases as determined by CT scan or MRI evaluation during screening or at prior radiographic assessments - Leptomeningeal disease - Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but not clinically stable for = 2 weeks prior to Cycle 1, Day 1 - Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment, with certain exceptions - Acute toxicities from previous therapy that have not resolved to Grade = 1, except for alopecia - Pregnant and lactating women - Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease - Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication - Significant cardiovascular disease within 3 months prior to Cycle 1, Day 1 - Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 - Severe infections within 4 weeks prior to Cycle 1, Day 1 - Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day - Active tuberculosis - Positive test for HIV - Patients with a positive hepatitis B surface antigen [HBsAg] test at screening or hepatitis C - Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study - History of autoimmune disease, except treated/stable autoimmune hypothyroidism or controlled type 1 diabetes mellitus on a stable insulin regimen. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are permitted provided that they meet certain pre-specified conditions. - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Prior allogeneic bone marrow transplantation or prior solid organ transplantation - History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan - Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study treatment or within 5 months after the last dose of atezolizumab - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies - Treatment with systemic immunostimulatory agents or with an investigational agent within 4 weeks or five half-lives of the drug prior to Cycle 1, Day 1 - Treatment with systemic corticosteroids or other systemic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Efficacy: to evaluate the percentage of patients who do not experience radiographic disease progression during the first 24 weeks of treatment with Atezolizumab, the percentage of patients that achieve an objective response, the best response achieved, the duration of response; the clinical benefit rate, the progression-free survival and time to progression [all these variables will be evaluated according to both RECIST v1.1 and modified RECIST (latter also NPR at 18 weeks), or disease-specific criteria for prostate cancer and malignant pleural mesothelioma], and overall survival. • Safety: safety and tolerability, immunogenic potential • Pharmacokinetics;Primary end point(s): 1. To evaluate non-progression rate (NPR) at 18 weeks in patients with advanced solid tumors treated with Atezolizumab, defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) as assessed by the Investigator according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) or according to disease-specific criteria for prostate cancer and malignant pleural mesothelioma;Main Objective: • To evaluate the percentage of patients who do not experience radiographic disease progression during the first 18 weeks of treatment with Atezolizumab.;Timepoint(s) of evaluation of this end point: 1. 18 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Efficacy: To evaluate NPR at 24 weeks, overall response rate (ORR), best overall response (BOR), clinical benefit rate (CBR), duration of response (DOR), time to tumor progression (TTP) and progression-free survival (PFS), as assessed by the Investigator using RECIST v1.1 and modified RECIST (latter also NPR at 18 weeks) or by disease-specific criteria for prostate cancer and malignant pleural mesothelioma. Overall survival (OS). 2. Safety: incidence, nature, and severity of adverse events, incidence of anti-atezolizumab antibodies, mean dose and number of cycles of atezolizumab 3. Pharmacokinetics: maximum and minimum serum atezolizumab concentrations;Timepoint(s) of evaluation of this end point: 1. Efficacy: 18 and 24 weeks (NPR), up to 24 months (OS). 2. Safety: up to 24 months. 3. Pharmacokinetics: Cmax at 30 minutes after tend of infusion on Day 1 of Cycle 1; Cmin up to 24 months. | — |
Countries
Austria, Brazil, Canada, China, Denmark, Finland, France, Germany, Ireland, Italy, Netherlands, Norway, Poland, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann La Roche Ltd
Outcome results
None listed