On March 4, 2026 INOVIO (NASDAQ: INO), and Akeso, Inc. (9926.HK) ("Akeso") reported that they 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 GBM. The combination therapy will be studied as a part of INSIGhT, the innovative 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 quickly and efficiently find new treatments for GBM. Dosing in the combination therapy trial is expected to begin in the second half of 2026.
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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 tumor antigens and driving T cell infiltration into the glioblastoma tumor 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 multicenter 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 (IO).
Dr. 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."
Dr. 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, PhD, founder, chairwoman, president, and Chief Executive Officer 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 centers 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.
About INSIGhT
The INdividualized Screening trial of Innovative Glioblastoma Therapy (INSIGhT) is investigating novel treatments in patients with newly diagnosed GBM. INSIGhT uses a shared control arm to test multiple investigational therapies at one time, with each arm independently compared only to the control. The arm of the trial that involves the collaboration between INOVIO and Akeso will investigate the safety and efficacy of INO-5412 in combination with cadonilimab in patients with histologically confirmed intracranial glioblastoma or gliosarcoma. Dosing is expected to begin in the second half of 2026. For more information about the clinical study, see www.clinicaltrials.gov, identifier NCT02977780.
About GBM
Glioblastoma (GBM) is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, with few therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months in patients with an unmethylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter and the median progression-free survival is approximately 4 to 6 months. The estimated annual incidence of GBM in the U.S. is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.
About INO-5412
INO-5412 is an investigational DNA medicine that combines INO-5401 and INO-9012 into a single vial as a potentially powerful cancer immunotherapy particularly when given in combination with checkpoint inhibitors. INO-5401 plus INO-9012 has been previously investigated as a potential therapeutic treatment targeting a number of cancers, including GBM and cancers exhibiting BRCA1 and BRCA2 mutations. Data from an ongoing Phase 2 trial in newly diagnosed GBM patients, highlighted in a 2022 oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), demonstrated that INO-5401 plus INO-9012 in combination with a PD-1 checkpoint inhibitor elicited robust immune responses that potentially correlated with enhanced survival. (Reardon D. et al, ASCO (Free ASCO Whitepaper) 2022).
INO-5401 encodes for INOVIO’s SynCon antigens for hTERT, WT1, and PSMA, which are antigens The National Cancer Institute has highlighted as important targets and designated as high priorities for cancer immunotherapy development. These three antigens have been reported to be over-expressed and often mutated in a variety of human cancers, including GBM. INO-9012 encodes for IL-12, which is a T cell immune activator.
About Cadonilimab
Cadonilimab, independently developed by Akeso, is the world’s first PD-1/CTLA-4 bispecific immuno-oncology therapy. It has been approved and reimbursed in China for three indications: recurrent/metastatic cervical cancer after platinum-based chemotherapy failure, first-line gastric cancer, and first-line cervical cancer. The drug has also been investigated in over 30 clinical trials spanning more than 20 tumor types. Currently, 11 Phase III or registrational trials are ongoing, with three already having met primary endpoints. With a novel dual-targeting mechanism against PD-1 and CTLA-4, cadonilimab demonstrates superior efficacy and a favorable safety profile compared to combination therapies. It has shown strong anti-tumor activity regardless of PD-L1 status and holds breakthrough potential in IO-resistant and immunologically "cold" tumors.
(Press release, Inovio, MAR 4, 2026, View Source [SID1234663247])