Inovio Pharmaceuticals has started a Phase Ib/II clinical trial to assess the combination of its INO-5401 and INO-9012 with Genentech’s atezolizumab (Tecentriq) to treat advanced bladder cancer.
INO-5401 is a T cell activating immunotherapy that encodes multiple antigens, while INO-9012 is an immune activator encoding IL-12 and atezolizumab is a PD-L1 checkpoint inhibitor.
The multi-centre, open-label Phase Ib/II trial will investigate the safety, clinical efficacy and immune response of the combination in around 80 subjects with advanced unresectable or metastatic urothelial carcinoma (UC).
Majority of the participants will constitute patients who have previously failed to achieve meaningful response with the monotherapy of a PD-L1 checkpoint inhibitor.
Inovio Pharmaceuticals president and CEO Dr Joseph Kim said: “Combining INO-5401 with Tecentriq may provide a synergistic therapeutic effect as a result of generating high levels of activated T cells and simultaneously inhibiting PD-L1.
“Bladder cancer has often been described as an immunogenic tumour, and here our approach is to augment the anti-PD-1/PD-L1 driven efficacy by further enhancing the T cells against the tumour in a cancer antigen-specific manner.”
The primary aim of the trial is to investigate the benefit of combining a checkpoint inhibitor with a DNA-based immunotherapeutic and T cell activator for treating bladder cancer, which is reported to have less options and poor treatment outcomes.
INO-9012 and INO-5401, along with atezolizumab are expected to deliver a synergistic therapeutic effect with high levels of activated T cells and concurrent PD-L1 inhibition.
Inovio also plans to carry out immunologic analyses to gain further understanding of checkpoint inhibition and T cell activation mechanisms in the disease.