INOVIO and Akeso, Inc. have entered into a clinical trial collaboration and supply agreement to evaluate INO-5412, INOVIO’s DNA immunotherapy candidate, in combination with cadonilimab, Akeso’s first-in-class PD-1/CTLA-4 bispecific antibody, for the potential treatment of glioblastoma (GBM).
The combination therapy will be studied as a part of INSIGhT, the phase 2 adaptive platform trial sponsored by the Dana-Farber Cancer Institute and conducted with Mass General Brigham Cancer Care, Inc., which is designed to find new treatments for GBM. Dosing in the combination therapy trial is expected to begin in the second half of 2026.
INO-5412 is composed of INO-5401 and T cell immune activator INO-9012. When combined with a checkpoint blockade, targeted DNA immunotherapy has the potential to overcome the challenges of immune checkpoint therapy alone by stimulating an immune response against tumour antigens and driving T cell infiltration into the glioblastoma tumour microenvironment. In an ongoing phase 2 trial in newly diagnosed GBM patients, INO-5401 plus INO-9012 in combination with a PD-1 checkpoint inhibitor elicited robust immune responses that potentially correlate with enhanced survival. The novel combination of INO-5412 with cadonilimab to treat GBM builds on this promising data and could potentially benefit patients by providing additional checkpoint inhibition through CTLA-4 binding.
Cadonilimab has received marketing approval in China for several indications, including first-line gastric cancer, first-line cervical cancer, and second/third-line cervical cancer, demonstrating effectiveness irrespective of PD-L1 expression status. As the world’s first approved bispecific antibody for cancer immunotherapy developed in China, its clinical value is well-established through real-world application and validation across multiple phase 3 trials. The drug is currently involved in over 11 phase 3/registration clinical studies. Among these are two international multicentre trials: a phase 3 registrational trial for the first-line treatment of gastric cancer, and a phase 2 registrational trial for the second-line treatment of liver cancer in patients who exhibit resistance to immune checkpoint inhibitors.
David Reardon, director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School said: “The INSIGhT trial was designed to help quickly advance cutting-edge treatments for GBM, the most common and aggressive form of brain cancer for which there are few effective treatments currently available or in development. We are excited to include INOVIO and Akeso’s novel combination immunotherapy in the trial and welcome their efforts to help improve potential outcomes for patients.”
Michael Sumner, INOVIO’s chief medical officer, said: “This collaboration is an important step forward for our cancer immunotherapy research and we are delighted to partner with two trailblazing organizations to advance this promising candidate in our late-stage clinical pipeline. Combining INO-5412 with Akeso’s novel checkpoint modality represents an important evolution of our research in GBM, builds on our previous data showing the potential to improve patient outcomes and highlights our ongoing commitment to advancing innovative treatments for diseases with significant unmet need.”
Yu (Michelle) Xia, founder, chairwoman, president, and CEO of Akeso, said: “We are truly excited to collaborate with INOVIO for the treatment of GBM. We are advancing cadonilimab worldwide through Akeso’s ‘in-house innovation + global partnership’ strategy to realize its breakthrough clinical benefits for patients all around the world across multiple cancer types. By collaborating with INOVIO, we aim to harness the benefit of combining INOVIO’s DNA medicine with cadonilimab’s dual checkpoint inhibition for the treatment of GBM, a particularly challenging central nervous system malignancy. We also look forward to working with one of the world’s leading cancer centres in the clinical development of the new cadonilimab and INO-5412 combination treatment for GBM.”
Under the terms of the agreement, INOVIO and Akeso will provide support for the INSIGhT study, including supplying their respective therapeutic products, while the investigative sponsors will oversee the day-to-day clinical operations.