solide tumoren Cancer solid tumors
Conditions
Interventions
Patients eligible for participation in the study will be treated with RO6958688
and atezolizumab. Patients will receive RO6958688 every week (QW) or every 3
weeks (Q3W) and atezolizumab every 3 week
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age * 18 years - Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in patients who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy. - Radiologically measurable and clinically evaluable disease (as per RECIST v1.1 - previously irradiated lesions should not be counted as target lesions) - Life expectancy of * 12 weeks and LDH levels
Exclusion criteria
Exclusion criteria: - Active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments - Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for * 2 weeks prior to enrolment - Leptomeningeal disease - Patients with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated. - Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome - Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug - Known history of autoimmune disease - patients with bilateral lung lesions and dyspnea and/or SaO2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety outcome measures The safety outcome measures for this study are: * Incidence and nature of DLTs * Incidence and severity of adverse events and IRRs and cytokine-release syndrome symptoms * Incidence of laboratory abnormalities (hematology testing, coagulation, serum chemistries, and urinalysis) * Incidence of ADAs (anti-atezolizumab antibodies and anti-RO6958688 antibodies) formation, detection of cytokine release and potential correlation with PK, PD, safety, and efficacy parameters * Incidence of autoantibodies (anti-nuclear antibody, anti-double-stranded DNA, cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic antibody) in comparison to baseline * Changes in vital signs, physical findings and ECG findings. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Outcome Measures Pharmacokinetic (PK) concentration data of RO6958688 and atezolizumab will be summarized with the use of descriptive statistical methods Pharmacodynamic Outcome Measures The PD outcome measures for this study are the following and will be examined in patients enrolled in both Parts I and II: * Whole blood samples: Peripheral blood immune cells will be assessed with respect to the changes in the characteristics of lineage (CD4+ T cells, CD8+ T cells, natural killer [NK] cells, monocytes, T-regulatory cells, and B cells), activation (including but not limited to CD25, CD69, etc.), and differentiation (including but not limited to CD45RO Ki67, PD1, TIM3, ICOS, etc.). * determination of TCR V* sequencing (the CDR3-TCR beta chain repertoire) and TCR V* diversity . * Serum or plasma samples: PD biomarkers such as cytokines and inflammation markers. * Tumor biopsy: Biopsies will be assessed centrally for changes in immune cell numbers and activation characteristics as well as changes in tumor markers such as PD-L1. * Positron Emission Tomography (PET): Baseline and on-treatment 2-[18F]-Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) will be collected to determine changes in glucose metabolism of the tumor lesions. * Original or archival tumor: Potential predictive/prognostic biomarkers such as MMR status and CEA expression will be confirmed on archival tumor, if available, or from the freshly obtained biopsy samples. These measurements will assess the RO6958688 and atezolizumab CEA change over the course of the disease and the stability of the measurements. | — |
Countries
Netherlands
Outcome results
None listed