INOVIO and Akeso Partner to Test Novel DNA-Bispecific Antibody Combination for Glioblastoma Treatment
核心洞察
INOVIO and Akeso (搜索) have entered a clinical collaboration to evaluate INO-5412 (搜索) combined with cadonilimab for treating glioblastoma (搜索), the most aggressive form of brain cancer (搜索).
The combination therapy will be studied in the Phase 2 INSIGhT adaptive platform trial sponsored by Dana-Farber Cancer Institute, with dosing expected to begin in the second half of 2026.
The study builds on positive Phase 2 results for INO-5401 in GBM patients, adding cadonilimab's dual PD-1 (搜索)/CTLA-4 (搜索) checkpoint inhibition to potentially enhance treatment efficacy.
INOVIO and Akeso (搜索) have announced a clinical trial collaboration to evaluate a novel combination therapy for glioblastoma (搜索) (GBM), combining INOVIO's DNA immunotherapy candidate INO-5412 (搜索) with Akeso's first-in-class PD-1 (搜索)/CTLA-4 (搜索) bispecific antibody cadonilimab. The combination will be studied as part of the INdividualized Screening trial of Innovative Glioblastoma Therapy (INSIGhT), a Phase 2 adaptive platform trial sponsored by the Dana-Farber Cancer Institute.
Addressing Critical Unmet Need in Brain Cancer
Glioblastoma (搜索) represents the most common and aggressive type of brain cancer (搜索), with an extremely poor prognosis. The median overall survival for patients receiving standard of care therapy is approximately 15 months in patients with an unmethylated MGMT 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, with a median age at diagnosis of 65 years.
Dr. David Reardon, Director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School, emphasized the urgent need for new treatments: "The INSIGhT trial was designed to help quickly advance cutting-edge treatments for GBM, the most common and aggressive form of brain cancer (搜索) for which there are few effective treatments currently available or in development."
Building on Promising DNA Immunotherapy Data
The collaboration builds on previously reported positive Phase 2 results involving INO-5401 in GBM patients. INO-5412 (搜索) is composed of INO-5401 and T cell immune activator INO-9012. 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), demonstrated that INO-5401 plus INO-9012 in combination with a PD-1 (搜索) checkpoint inhibitor elicited robust immune responses that potentially correlated with enhanced survival.
INO-5401 encodes for INOVIO's SynCon® antigens for hTERT, WT1 (搜索), and PSMA (搜索), 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 (搜索), which is a T cell immune activator.
First-in-Class Bispecific Antibody Platform
Cadonilimab brings a unique dual-targeting mechanism to the combination. As the world's first approved bispecific antibody for cancer immunotherapy developed in China, cadonilimab has received marketing approval in China for several indications, including first-line gastric cancer (搜索), first-line cervical cancer (搜索), and second/third-line cervical cancer, demonstrating effectiveness irrespective of PD-L1 expression status.
The drug is currently involved in over 11 Phase 3/registration clinical studies, including two international multicenter trials: a Phase 3 registrational trial for the first-line treatment of gastric cancer (搜索), and a Phase 2 registrational trial for the second-line treatment of liver cancer (搜索) in patients who exhibit resistance to immune checkpoint inhibitors. With its novel dual-targeting mechanism against PD-1 (搜索) and CTLA-4 (搜索), cadonilimab demonstrates superior efficacy and a favorable safety profile compared to combination therapies and has shown strong anti-tumor activity regardless of PD-L1 status.
Strategic Rationale for Combination Approach
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 (搜索) tumor microenvironment. The novel combination of INO-5412 (搜索) with cadonilimab could potentially benefit patients by providing additional checkpoint inhibition through CTLA-4 (搜索) binding.
Dr. Michael Sumner, INOVIO's Chief Medical Officer, stated: "Combining INO-5412 (搜索) with Akeso (搜索)'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."
Trial Design and Timeline
The INSIGhT trial uses a shared control arm to test multiple investigational therapies at one time, with each arm independently compared only to the control. The arm involving the INOVIO-Akeso (搜索) collaboration will investigate the safety and efficacy of INO-5412 (搜索) in combination with cadonilimab in patients with histologically confirmed intracranial glioblastoma (搜索) or gliosarcoma. Dosing in the combination therapy trial is expected to begin in the second half of 2026.
Yu (Michelle) Xia, PhD, founder, chairwoman, president, and Chief Executive Officer of Akeso (搜索), expressed enthusiasm for the partnership: "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."
Under the terms of the agreement, INOVIO and Akeso (搜索) 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.