PLYMOUTH MEETING, Pennsylvania & HONG KONG, March 4, 2026
INOVIO Pharmaceuticals and Akeso Inc. have announced a strategic clinical collaboration to develop a novel combination immunotherapy for glioblastoma (GBM), the most aggressive and common form of brain cancer. The partnership will evaluate INOVIO’s DNA-based immunotherapy candidate INO-5412 in combination with Akeso’s bispecific antibody cadonilimab, a first-in-class PD-1/CTLA-4 dual checkpoint inhibitor. The therapy will be investigated within the INSIGhT Phase 2 adaptive platform trial, an innovative clinical research initiative sponsored by the Dana-Farber Cancer Institute designed to accelerate the development of new treatments for glioblastoma. The collaboration aims to enhance immune responses against tumors and potentially improve survival outcomes in patients with this devastating disease, for which treatment options remain extremely limited.
Novel Immunotherapy Combination Targets Aggressive Brain Cancer
Glioblastoma remains one of the most challenging cancers to treat due to its rapid progression, resistance to conventional therapies, and highly immunosuppressive tumor microenvironment. The new collaboration focuses on combining two complementary immunotherapy technologies that may overcome these challenges and improve treatment effectiveness.
INOVIO’s investigational therapy INO-5412, composed of INO-5401 and the immune activator INO-9012, is designed to stimulate a targeted immune response against tumor-associated antigens including hTERT, WT1, and PSMA, which are frequently overexpressed in glioblastoma and other cancers. These antigens have been identified by cancer researchers as key targets for immunotherapy development.
When administered with checkpoint inhibitors, DNA-based immunotherapies such as INO-5412 can potentially enhance immune cell infiltration into tumors and activate T-cell responses, enabling the body’s immune system to recognize and attack cancer cells more effectively. Previous Phase 2 data involving INO-5401 combined with a PD-1 checkpoint inhibitor demonstrated robust immune responses that correlated with improved survival signals in glioblastoma patients, providing the scientific rationale for the new combination therapy trial.
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INSIGhT Platform Trial Accelerates Innovative GBM Research
The INdividualized Screening trial of Innovative Glioblastoma Therapy (INSIGhT) represents a groundbreaking adaptive clinical trial platform designed to rapidly test multiple investigational therapies simultaneously for patients with newly diagnosed glioblastoma. By using a shared control arm and evaluating several treatment strategies in parallel, the platform aims to accelerate the identification of effective therapies for one of the most difficult cancers to treat.
Under the collaboration agreement, INOVIO and Akeso will supply their investigational products while the study’s academic investigators oversee clinical operations. Dosing for the combination therapy arm is expected to begin in the second half of 2026, marking a key milestone in advancing innovative immunotherapy approaches for brain cancer.
Akeso’s investigational drug cadonilimab plays a critical role in the combination strategy. The therapy is the world’s first approved PD-1/CTLA-4 bispecific antibody for cancer immunotherapy, designed to enhance immune checkpoint blockade by simultaneously targeting two critical immune pathways. Clinical studies have demonstrated that cadonilimab can produce strong anti-tumor activity across multiple cancers while maintaining a favorable safety profile, supporting its inclusion in combination immunotherapy trials.
Potential Breakthrough in Immunotherapy for Glioblastoma
Glioblastoma remains a devastating disease with a median overall survival of approximately 15 months despite standard treatment, which typically includes surgery, radiation, and chemotherapy. The cancer’s resistance to treatment and ability to evade immune responses make it a priority target for next-generation immunotherapies.
By combining DNA-based immunotherapy with dual checkpoint inhibition, researchers aim to activate multiple components of the immune system simultaneously. This strategy could potentially enhance T-cell activation, improve immune cell infiltration into tumors, and overcome resistance mechanisms that limit the effectiveness of current therapies.
Scientists involved in the INSIGhT trial believe that integrating innovative technologies such as DNA medicines and bispecific antibodies may represent the future of precision immuno-oncology. If successful, the INOVIO–Akeso collaboration could lead to new treatment options for patients with glioblastoma and potentially other difficult-to-treat cancers, highlighting the growing importance of collaborative research partnerships in advancing cancer therapies.
As clinical research continues to evolve, the development of advanced immunotherapy combinations may ultimately transform the treatment landscape for glioblastoma and bring renewed hope to patients facing one of the most aggressive forms of cancer.
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Source: INOVIO Pharmaceuticals and Akeso Inc. press release
