INOVIO–Akeso Collaboration Advances Multimodal GBM Immunotherapy

INOVIO, a US-based clinical-stage biotechnology company, and Akeso, a China-based biopharmaceutical company, announced a clinical trial collaboration on March 4, 2026, in which the companies plan to evaluate a combination immunotherapy regimen for glioblastoma (GBM). Their aim is to integrate a targeted DNA immunotherapy platform with dual immune checkpoint inhibition.¹

The collaboration will assess INO-5412, comprising INO-5401 and the interleukin-12 (IL-12)–encoding immune activator, INO-9012, in combination with cadonilimab, a programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte associated antigen 4 (CTLA-4) bispecific antibody. The regimen will be investigated within a Phase II adaptive platform trial known as the INdividualized Screening trial of Innovative Glioblastoma Therapy (INSIGhT), sponsored by Dana-Farber Cancer Institute and conducted with Mass General Brigham Cancer Care. Initial dosing is expected to begin in the second half of 2026.

"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,” said David Reardon, MD, director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School, in a company press release.¹ “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."

How could DNA immunotherapy enhance checkpoint blockade in GBM?

GBM remains the most common and aggressive primary brain malignancy, with limited therapeutic advancement over the past decade. Median overall survival remains approximately 15 months for patients with unmethylated O⁶-methylguanine-DNA methyltransferase promoter status under standard-of-care treatment, underscoring the need for novel immune-modulating strategies capable of overcoming tumor microenvironment resistance.²

INO-5412 is designed to encode tumor-associated antigens hTERT, WT1, and PSMA, which are frequently overexpressed in GBM, alongside IL-12 to promote T-cell activation. The strategy aims to prime tumor-specific immune responses and improve T-cell infiltration into the immunologically suppressive GBM microenvironment, according to the companies.¹

Previous Phase II data involving INO-5401 plus INO-9012 in combination with PD-1 inhibition demonstrated immune activation associated with signals suggesting potential survival benefit in newly diagnosed GBM patients. The addition of cadonilimab introduces simultaneous PD-1 and CTLA-4 blockade, which potentially amplifies checkpoint modulation beyond single-agent PD-1 inhibition.¹

Cadonilimab is a bispecific antibody that targets both PD-1 and CTLA-4 pathways. It is approved in China for multiple oncology indications, including cervical and gastric cancers. It has demonstrated activity irrespective of PD-L1 expression status and is currently under evaluation in multiple Phase III or registrational studies globally.

By combining antigen-specific immune priming with dual checkpoint inhibition, the collaboration seeks to evaluate whether coordinated immune activation and suppression reversal may overcome the limited efficacy observed with checkpoint inhibitors alone in GBM.

“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," said Michael Sumner, MBBS, INOVIO’s chief medical officer, in the release.¹

Why is the adaptive platform model significant for GBM drug development?

“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,” said Yu (Michelle) Xia, PhD, founder, chairwoman, president, and CEO of Akeso, in the release.¹ “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."

INSIGhT is an adaptive, multi-arm Phase II platform trial using a shared control arm to evaluate multiple investigational therapies concurrently. Each experimental arm is independently compared to a control, enabling more efficient screening of potential treatments in newly diagnosed GBM.

Under the collaboration, INOVIO and Akeso will provide study drug supply and support, while investigative sponsors oversee trial execution. The combination arm will evaluate safety and efficacy in patients with histologically confirmed intracranial glioblastoma or gliosarcoma.

As immunotherapy strategies in neuro-oncology increasingly incorporate multi-mechanistic approaches, platform trials such as INSIGhT may play a central role in determining whether combinatorial immune modulation can shift long-standing survival limitations in GBM.^1,3

References

1. INOVIO. INOVIO and Akeso Announce Clinical Collaboration to Advance Novel Combination Therapy for Glioblastoma (GBM). Press Release. March 4, 2026.
2. Sipos D, Raposa BL, Freihat O, et al. Glioblastoma: Clinical Presentation, Multidisciplinary Management, and Long-Term Outcomes. Cancers (Basel). 2025;17(1):146. doi: 10.3390/cancers17010146
3. Saraf A, Trippa L, Rahman R. Novel Clinical Trial Designs in Neuro-Oncology. Neurotherapeutics. 2022;19(6):1844-1854. doi: 10.1007/s13311-022-01284-x