Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumour Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment

Official Title

An Open-Label, Multicentre, Phase Ib Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumour Activity Of RO7122290, A Fibroblast Activation Protein-A (FAP) Targeted 4-1BB Ligand (CD137L), In Combination With Cibisatamab With Obinutuzumab Pre-Treatment, In Participants With Previously Treated, Metastatic, Microsatellite-stable Colorectal Adenocarcinoma With High CEACAM5 Expression

Summary:

This is an open-label, multicentre, Phase Ib study to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) in the weekly (QW) and/or every 3 weeks (Q3W) regimens, safety, tolerability, PK, immunogenicity, PD profile and to evaluate preliminary anti-tumour activity of RO7122290 in combination with cibisatamab Q3W after pretreatment with obinutuzumab, in participants with previously treated metastatic, microsatellite-stable colorectal adenocarcinoma with high CEACAM5 expression

Trial Description

Primary Outcome:

• Part I: Occurrence of dose-limiting toxicities
• Percentage of Participants with Adverse Events

• Serum concentration of RO7122290 over time
• Plasma concentration of RO7122290 over time
• Maximum concentration (Cmax) of RO7122290
• Time of maximum concentration (Tmax) of RO7122290
• Clearance (CL) of RO7122290
• Volume of distribution (V) of RO7122290
• Area under the curve (AUC) of RO7122290
• Half-life (t1/2) of RO7122290
• Serum concentration of Cibisatamab over time
• Plasma concentration of Cibisatamab over time
• Maximum concentration (Cmax) of Cibisatamab
• Time of maximum concentration (Tmax) of Cibisatamab
• Clearance (CL) of Cibisatamab
• Volume of distribution (V) of Cibisatamab
• Area under the curve (AUC) of Cibisatamab
• Half-life (t1/2) of Cibisatamab
• Serum concentration of Obinutuzumab over time
• Plasma concentration of Obinutuzumab over time
• Maximum concentration (Cmax) of Obinutuzumab
• Time of maximum concentration (Tmax) of Obinutuzumab
• Clearance (CL) of Obinutuzumab
• Volume of distribution (V) of Obinutuzumab
• Area under the curve (AUC) of Obinutuzumab
• Half-life (t1/2) of Obinutuzumab
• Percentage of Participants with RO7122290 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
• Percentage of Participants with Cibisatamab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
• Percentage of Participants with Obinutuzumab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
• Treatment-induced change on T-cell proliferation (CD8/Ki67)
• Treatment-induced change on T-cell activation (CD8/4-1BB)
• Treatment-induced change on tumour necrosis factor alpha (TNF-alpha) levels
• Treatment-induced change on interferon gamma (IFN-gamma) levels
• Treatment-induced change on Interleukin (IL)-2 levels
• Treatment-induced change on Interleukin (IL)-6 levels
• Treatment-induced change on Interleukin (IL)-8 levels
• Treatment-induced change on Interleukin (IL)-10 levels
• Treatment-induced change on Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels
• Objective response rate (ORR) defined as complete response (CR) + partial response (PR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
• Disease control rate (DCR); defined as response rate (RR) + stable disease (SD) according to the Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
• Duration of response (DoR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
• Progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
• Change on CEACAM5 tumour expression levels
• Change on CEA tumour expression levels
• Change on FAP tumour expression levels
• Change on 4-1BB tumour expression levels

View this trial on ClinicalTrials.gov