CEA positieve solide tumoren advanced and/or metastatic CEA positieve solide tumors/organ tumors
Conditions
Interventions
Patients who are eligible will be treated with RO6895882 according the study
specific schedule as shown in appendix 1 of the protocol p. 106-118.
Substudy BP28920/IMG
Patients who are eligible will
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: *Signed informed consent. *Confirmed advanced and/or metastatic solid tumor, with confirmed progression at baseline, for whom no standard treatment is available. *Radiologically measurable and clinically evaluable disease. *Adequate hematological function: neutrophil count of * 1.5 x 109 cells/L, platelet count of * 100,000/µl, Hb * 10 g/dL (6.2 mmol/L), including lymphocytes within normal limits. *Adequate liver function: Total Bilirubin * 1.5 x ULN (excluding Gilbert*s Syndrome, see below), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) * 2.5 x ULN (in case of liver metastases: * 5 x ULN). *Adequate renal function: serum creatinine * 1.5 ULN or creatinine clearance by Cockcroft Gault formula [see Appendix X] * 50 mL/min for patients in whom, in the investigator*s judgment, serum creatinine levels do not adequately reflect renal function. *Locally confirmed CEA expression in tumor tissue (>20% of tumor cells staining with at least moderate intensity);Extra for Imaging substudy: At least one non-liver tumor lesion that is assessable by PET imaging
Exclusion criteria
Exclusion criteria: *History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before screening . *Patients with a second malignancy in the last 5 years (with the exception of basal cell carcinoma). *Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases. ;Extra for Imaging substudy: Patients who have had a hypersenitivity reaction to 2-[18F]Fluoro-2-deoxyglucose (FDG)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * to describe the safety profile for qW, q2W and q3W regimens. * to determine the Maximum Tolerated Dose (MTD), if achieved (all regimens) * to describe the pharmacokinetics (PK) of single-agent RO6895882. Substudy BP28920/IMG To investigate the in vivo biodistribution and organ pharmacokinetics of radioactivity (89Zr) at two doses: 6 mg (or a lower dose should 6 mg not be considered safe in Part I of the main study BP28920) and at the maximum tolerated dose (MTD) or a lower dose with equivalent pharmacodynamic (PD) effects as determined for the q2W regimen in Part II of the main study BP28920. Substudy BP28920/ obinutuzumab: Proportion of patients without ADA titer at Cycle 4 To evaluate the safety and tolerability of administration of obinutuzumab given prior to treatment with RO6895882 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part I (Single Ascending Dose): * to characterize the pharmacodynamics (PD) of single dose RO6895882 on peripheral blood cells by determining sCD25 Part II and Part III (Dose Escalation Monotherapy and MTD expansion): * to characterize PD effects (number, proliferation and activation of immune cells) of multiple doses of RO6895882 on peripheral blood cells * to determine the changes in PD biomarkers (proliferation, activation and infiltration of immune cells and PD-L1 expression) associated with RO6895882 treatment in tumors * to obtain preliminary anti-tumor activity data of objective overall response rate (ORR), disease control rate (DCR; defined as RR + stable disease [SD]) and progression-free survival (PFS) according to RECIST v1.1 criteria, of single-agent RO6895882. Exploratory Objectives * to explore the PD effects and duration of PD response for the qW, q2W and q3W regimens based on an increase in activated CD8+ tumor infiltrating lymphocytes (TIL) * to explore at different doses the relationship between exposure - PD and clinical effects of RO6895882 * to obtain preliminary anti-tumor activity data of objective overall response rate (ORR), disease control rate (DCR; defined as RR + SD) and progression-free survival (PFS) according to immune-related Response Criteria (irRC), of single-agent RO6895882 * to investigate the correlation between genetic markers from baseline blood samples with response, including but not limited to KIR and HLA genotypes * to investigate potential predictive PD biomarkers from paired tumour biopsies (including, but not limited to CD3, CD4, CD8) Substudy BP28920/IMG 1) To describe the relationship between tumor targeting and observed pharmacodynamic effects in the corresponding tumor lesions using: - changes in PD biomarkers - dualphase 18F-FDG-PET to measure local RO6895882-induced inflammatory response and anti-neoplastic effects 2) To describe the safety of RO6895882. Substudy BP28920/ obinutuz | — |
Countries
Netherlands
Outcome results
None listed