Atezolizumab, Rituximab, Gemcitabine and Oxaliplatin in Patients With Relapsed or Refractory DLBCL Not Suitable for High-dose Therapy

Summary

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Description

Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. The R-GemOx regimen has been adopted by many sites internationally as therapy for older patients or comorbid pati...

Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. The R-GemOx regimen has been adopted by many sites internationally as therapy for older patients or comorbid patients with relapsed or refractory DLBCL and as a back-bone for the investigation of novel therapies in combination with chemotherapy. The cytotoxic T-lymphocyte co-receptor PD-1 has been extensively studied and is recognised to provide critical inhibitory signals that down-regulate T-cell function and provides a mechanism for immune evasion for tumours. PD-L1, the ligand of PD-1 is expressed on DLBCL tumour cells, along with infiltrating non-malignant cells, primarily macrophages, with PD-1 expressed on tumour infiltrating lymphocytes (TILs). Atezolizumab targets programmed PD-L1 on immune and tumour cells and prevents interaction with either PD-1 receptor or B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells. Interference of the PD-L1:PD-1 and PDL1:B7.1 interactions may enhance the magnitude and quality of the tumour-specific T-cell response through increased T-cell priming, expansion, and/or effector function. This study of atezolizumab in combination with rituximab, gemcitabine and oxaliplatin aims to address the unmet need of patients with relapsed and refractory DLBCL. It is based upon a sound mechanistic approach, investigating the activity of novel agents and will aim to compressively explore biomarkers of response. The primary objective will be to document the durability of anti-tumour activity in patients with relapsed or refractory DLBCL and to determine the safety and toxicity profile of the combination. A maintenance phase of atezolizumab has been added as this may induce an on-going T-cell response to neo-antigens released as a result of chemotherapy.

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