Inovio Pharmaceuticals has announced a clinical collaboration with Genentech, a member of the Roche Group, for advanced bladder cancer. The phase 1b/2 immuno-oncology trial will evaluate Genentech’s atezolizumab (Tecentriq) in combination with Inovio’s INO-5401, a T cell activating immunotherapy encoding multiple antigens, and INO-9012, an immune activator encoding IL-12.

The multi-center open-label trial will be managed by Inovio, and Genentech will supply atezolizumab. It is anticipated to start in 2017 and designed to evaluate the safety, immune response and clinical efficacy of the combination therapy in approximately 80 patients with advanced bladder cancer, specifically advanced unresectable or metastatic urothelial carcinoma (UC), the most common type of bladder cancer. The majority of the patients to be enrolled in the trial will have previously received and failed to demonstrate meaningful response to a checkpoint inhibitor alone. Thus the study will evaluate potential benefit of a checkpoint inhibitor combined with a DNA-based immunotherapeutic and T-cell activator within a bladder cancer patient population with very limited treatment options and poor outcomes. The immunologic analyses accompanying the study will provide further insight into mechanisms of checkpoint inhibition and T-cell activation in bladder cancer.

Nearly 430,000 new cases of urinary bladder cancer are diagnosed each year worldwide; it accounts for about 165,000 deaths worldwide annually. Advanced unresectable or metastatic UC remains a high unmet medical need as survival remains poor for most patients who experience disease progression or intolerance to treatment during or after platinum-containing chemotherapy. The approval of several checkpoint inhibitors for advanced unresectable or metastatic UC has improved response and survival rates for some patients, however, the majority of patients do not experience meaningful clinical responses to checkpoint inhibitor monotherapy.

Inovio’s INO-5401, an immunotherapy encoding multiple cancer antigens, is designed to generate and activate T-cells to many cancer types including bladder cancer. INO-9012, an immune activator encoding IL-12, is designed to amplify and accelerate T cell immune responses to INO-5401. Combining INO-5401/INO-9012 with atezolizumab may provide a synergistic therapeutic effect as a result of generating higher levels of activated T cells and simultaneously inhibiting PD-L1. Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

Dr. Joaquim Bellmunt, MD, PhD, Dana-Farber/Brigham and Women's Cancer Center Associate Professor, Harvard Medical School, said, “Urothelial carcinoma represents an area of high unmet need. Checkpoint inhibitors offer significant potential, however, only a proportion of patients respond to these therapies alone. Increasing evidence suggests that combinatorial approaches are needed and a combination of a checkpoint inhibitor with an immunotherapy that generates antigen-specific T cells may offer the potential for significantly increased benefit.”

Dr. J. Joseph Kim, Inovio's president and chief executive officer, said, “We are excited to collaborate with Genentech, a leader in the development of transformative products to treat cancer. I am a strong believer in combination immuno-oncology regimens employing an immunotherapy to generate significant antigen-specific killer T cells then blocking T cell suppression via checkpoint inhibition. We believe INO-5401 has significant potential as a cancer immunotherapeutic in combination with a checkpoint inhibitor to address the high unmet medical need for advanced bladder cancer patients and to provide meaningful benefit for checkpoint inhibitor refractory patients.”