colon cancer Colorectal adenocarcinoma
Conditions
Interventions
The investigational medicinal products(IMPs) for this study are:
- obinutuzumab (2000 mg single dose or 2 x 1000 mg split doses)
- cibisatamab (100 mg)
- RO7122290 (Part I starting dose will be 35 mg
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Histologically confirmed adenocarcinoma originating from the colon or rectum • Metastatic disease not amenable to local treatment • Availability of archival tumor tissue or tissue obtained from a fresh biopsy at screening (if archival tumor is not available) • Tumors that are MSS or MSI-low (microsatellite instable low), as determined by a certified laboratory • Experienced disease progression during or within 3 months following the last administration of approved standard therapies after patients have received at least 2 prior lines of treatment. • Eastern Cooperative Oncology Group Performance Status of 0 or 1 • Life expectancy of >= 12 weeks • Adequate cardiovascular, hematologic and hepatic function • Serum creatinine within normal limits or a calculated glomerular filtration rate of >= 60 mL/min/1.73 m2 for participants with serum creatinine levels above or below the institutional normal value • Serum albumin >=30 g/L (3.0 g/dL) • Lactate dehydrogenase
Exclusion criteria
Exclusion criteria: •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases •History of leptomeningeal disease •Non-irradiated tumor lesions > 2 cm at critical sites where tumor swelling induced by cibisatamab is expected to lead to significant complications •Dyspnea or peripheral capillary oxygen saturation 10 bilateral pulmonary lesions •Patients with pulmonary miliary metastatic pattern or pulmonary lymphangitic carcinomatosis •Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration •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 initiation of study treatment •History of progressive multifocal leukoencephalopathy (PML) •Uncontrolled tumor-related pain •Uncontrolled ascites requiring recurrent drainage procedures •Patients with pericardial effusion •Uncontrolled or symptomatic hypercalcemia •Active or history of autoimmune disease or immune deficiency •Active tuberculosis that has required treatment within 3 years prior to initiation of study treatment or latent tuberculosis. •Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study •History of malignancy other than CRC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate>90%) •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, or other disease with ongoing fibrosis •Known active infection, or latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens, or any major episode of infection requiring hospitalization or treatment with systemic antibiotics treatment must have been completed at least 4 and 2 weeks •Prior allogeneic stem cell or solid organ transplantation •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment •Active or history of autoimmune disease or immune deficiency •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins •Major surgery or significant traumatic injury <28 days prior to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Nature and frequency of dose-limiting toxicities (DLTs; Part I only) - Incidence, nature and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 with the exception of cytokine release syndrome (CRS), which is graded according to the ASTCT grading scale for CRS (with individual signs and symptoms of CRS graded separately using the CTCAE v5.0 grading scale) | — |
Secondary
| Measure | Time frame |
|---|---|
| - PK profiles and parameters derived for RO7122290, cibisatamab, and obinutuzumab, as appropriate, including but not limited to: - Serum/plasma concentrations - Maximum concentration (Cmax) - Time of maximum concentration (Tmax) - Clearance (CL) - Volume of distribution (V) - Area under the curve (AUC) - Half-life (t1/2) -Incidence and titer of RO7122290, cibisatamab, and obinutuzumab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline -PK profiles and parameters derived for RO7122290, cibisatamab, and obinutuzumab, as appropriate, including but not limited to: - Serum/plasma concentrations - Maximum concentration (Cmax) - Time of maximum concentration (Tmax) - Clearance (CL) - Volume of distribution (V) - Area under the curve (AUC) - Half-life (t1/2) -Incidence and titer of RO7122290, cibisatamab, and obinutuzumab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline Peripheral blood lymphocytes: -Treatment-induced change on T-cell proliferation (CD8/Ki67). - Objective response rate (ORR) defined as complete response (CR) + partial response (PR) - Disease control rate (DCR); defined as response rate (RR) + stable disease (SD) - Duration of response (DoR) - Progression-free survival (PFS) All according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | — |
Countries
Netherlands
Outcome results
None listed