Although acquired immunodeficiency syndrome-related mortality is decreasing with the introduction of effective antiretroviral therapy, it has been reported a significant increase in the proportion of non-acquired immunodeficiency syndrome defining malignancies in HIV infected patients, often associated with premature immunosenescence and exhaustion. It has been shown in murine models and humans that programmed cell death ligand 1 (PD-L1) and its receptor, programmed cell death 1 (PD-1) play an active and reversible role mediating T-cell exhaustion both in cancer and in chronic infections. Binding PD-1 to its ligand PD-L1negatively regulates T-cell response, leading to an exhausted phenotype on CD8+ T cells. Therefore, there is a potential of immunotherapeutic intervention targeting PD-1/PD-L1 in order to enhance anti tumoral immune responses as well as to facilitate viral eradication. Durvalumab (MEDI4736) is a human monoclonal antibody (MAb) of the immunoglobulin G1 kappa (IgG1κ) subclass that inhibits binding of programmed cell death ligand 1 (PD-L1) to programmed cell death 1 (PD-1; CD279) and CD80 (B7-1). Durvalumab has demonstrated in cancer patients a favorable safety profile with encouraging antitumor activity, but there are no data about tolerance or anti retroviral activity in HIV patients.
This is an ongoing multicenter, open-label, phase 2 study (EUDRACT: 2016-004524-38) whose primary objective is to assess the feasibility of durvalumab at the recommended dose of 1500 mg every 4 weeks in HIV-infected patients with solid tumors for which no additional oncologic standard treatment is available. As secondary objectives the response rate (RECIST 1.1 and irRECIST), duration of response, PFS and OS will be measured. Exploratory objectives include the assessment of antiviral activity by measuring the changes in the HIV viral reservoir, the residual viral replication and the composition and function of circulating T lymphocytes and the study of molecular predictive factors of antitumoral activity on pretreatment tumor samples.
Clinical trial identification
Legal entity responsible for the study
Spanish Lung Cancer Group
All authors have declared no conflicts of interest.