Two immunotherapies, INO–5401 and INO–9012, will be combined with immune checkpoint inhibitor Tecentriq (atezolizumab) in a Phase 1/2 trial to test the combo’s safety and effectiveness in treating advanced bladder cancer.
The trial, a result of collaboration between Inovio Pharmaceuticals and Genentech, will start this year and enroll 80 patients with unresectable or metastatic urothelial carcinoma, the most common type of bladder cancer.
“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,” Joaquim Bellmunt, MD, PhD, Dana–Farber/Brigham and Women’s Cancer Center associate professor at Harvard Medical School, said in a press release. “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.”
INO–5401 encodes the antigens for the WT1, hTERT, and PSMA proteins, which are expressed at high levels in several cancers. Antigens are parts of a protein that trigger an immune response in the body.
INO–9012 encodes the interleukin (IL)–12 protein, which triggers the activation and expansion of immune T–cells.
Combining INO–5401 and INO–9012 with a checkpoint inhibitor could simultaneously generate high levels of activated T–cells while removing the breaks imposed by tumor cells on immune cells. Tecentriq does the latter by inhibiting the PD–L1 protein, which binds to the PD–1 receptor on immune cells.
The upcoming multicenter, open–label trial is designed to assess the safety, immune response, and clinical effectiveness of the INO–4501/INO–9012/Tecentriq triple combo in advanced unresectable, or metastatic urothelial carcinoma.
Most participants will be patients who have already received an immune checkpoint inhibitor but did not respond to treatment. These patients have poor outcomes and very limited treatment options.
“We are excited to collaborate with Genentech, a leader in the development of transformative products to treat cancer,” said J. Joseph Kim, Inovio’s president and chief executive officer. “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,” he added.
Some 430,000 new cases of urinary bladder cancer are diagnosed globally each year.