Cue Biopharma has initiated dosing in a Phase 1b investigator-sponsored trial evaluating CUE-102 for recurrent glioblastoma multiforme (rGBM) at Dana-Farber Cancer Institute (DFCI). The open-label study (NCT06917885) represents a significant step forward in addressing one of the most challenging cancers to treat, with the first patient receiving adjuvant CUE-102 therapy.
Novel Immunotherapy Approach for Brain Cancer
The trial is led by David A. Reardon, MD, Clinical Director of the Center for Neuro-Oncology at DFCI and a recognized leader in brain cancer immunotherapy. The study aims to evaluate the tolerability and clinical activity of CUE-102 in patients with glioblastoma at first recurrence.
"Glioblastoma remains one of the most aggressive and hard-to-treat cancers, and as a result, there is a pressing need for more effective therapies," said Dr. Reardon. "Investigational treatments targeting WT1 in GBM have shown a potential correlation between expansion of antigen-specific T cells and survival."
CUE-102 is designed to activate and expand Wilms' Tumor 1 (WT1)-specific T cells by presenting the WT1 peptide to the WT1-specific T cell receptor. This mechanism targets tumor cells by activating WT1-specific T cells, which may improve clinical outcomes in recurrent glioblastoma.
Addressing Immunologically "Cold" Tumors
Matteo Levisetti, MD, chief medical officer at Cue Biopharma, highlighted the unique challenges posed by glioblastoma. "Glioblastoma is an immunologically 'cold' tumor representing a disadvantage for treatment with standard immunotherapies such as checkpoint inhibitors, but is known to express high levels of the Wilms' Tumor 1 oncofetal protein," he explained.
The company believes CUE-102's mechanism of action to preferentially activate and expand WT1 tumor-specific T cells has the potential to activate and generate an enhanced anti-tumor immune response against glioblastoma.
Promising Safety Profile from Previous Studies
CUE-102 has demonstrated encouraging results in earlier clinical development. In a Phase 1 open-label, dose escalation and expansion trial (NCT05360680), the drug showed anti-tumor activity and a favorable tolerability profile with no dose-limited toxicities observed in patients with late-stage colorectal, gastric/gastroesophageal junction, pancreatic and ovarian cancers that express WT1.
Significant Unmet Medical Need
Glioblastomas represent the most common primary cancer of the brain and the most aggressive type of brain tumor. Approximately 13,000 new cases are diagnosed each year in the United States. The prognosis remains poor, with the most common length of survival following diagnosis being 12 to 15 months, and fewer than 3 to 5 percent of people surviving longer than five years.
Innovative Platform Technology
CUE-102 is the second clinical drug candidate from Cue Biopharma's CUE-100 series of interleukin 2 (IL-2)-based biologics. The CUE-100 series consists of Fc-fusion biologics that present two signals to T cells: a tumor-specific peptide linked to a major histocompatibility complex (pMHC) for selectivity and specificity, and a rationally engineered IL-2 molecule to trigger T cell activation.
The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.
WT1 is a well-recognized onco-fetal protein known to be over-expressed in a number of cancers, including solid tumors and hematologic malignancies, making it an attractive target for cancer immunotherapy approaches.
