On August 13, 2025 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively engage and modulate disease-specific T cells for the treatment of autoimmune disease and cancer, reported the initiation of an investigator sponsored trial (IST) in rGBM at the DFCI with the first patient in the trial having been dosed with CUE-102 (Press release, Cue Biopharma, AUG 13, 2025, View Source [SID1234655212]). The trial (NCT06917885) is a Phase 1b, open-label study of adjuvant CUE-102, the Company’s drug product candidate targeting Wilms’ Tumor 1 protein (WT1) expressing cancers. The principal investigator of the Phase 1b trial, David A. Reardon, MD, is the Clinical Director of the Center for Neuro-Oncology at DFCI and a leader in the field of immunotherapy for the treatment of brain cancer. The goal of the study is to evaluate the tolerability and clinical activity of CUE-102 in patients with GBM at first recurrence.

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"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. Investigational treatments targeting WT1 in GBM have shown a potential correlation between expansion of antigen-specific T cells and survival," said Dr. Reardon. "CUE-102 is designed to target tumor cells by activating WT1 specific T cells, which may improve clinical outcomes in recurrent GBM."

Matteo Levisetti, MD, chief medical officer at Cue Biopharma, added, "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. We believe the mechanism of action of CUE-102, 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. We are highly encouraged by the clinical data generated to date from the CUE-100 series, CUE-101 and CUE-102, and look forward to reporting results from this investigator sponsored trial."

About CUE-102
CUE-102 is Cue Biopharma’s second clinical drug candidate from the CUE-100 series of interleukin 2 (IL-2)-based biologics. It 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. WT1 is a well-recognized onco-fetal protein known to be over-expressed in a number of cancers, including solid tumors and hematologic malignancies. CUE-102 has demonstrated anti-tumor activity and a favorable tolerability profile with no dose limited toxicities observed in a Phase 1 open label, dose escalation and expansion trial (NCT05360680), for patients with late-stage colorectal, gastric/gastroesophageal junction, pancreatic and ovarian cancers that express WT1.

About Glioblastoma
Glioblastomas are the most common primary cancer of the brain and the most aggressive type of brain tumor. There are ~13,000 new cases diagnosed each year in the United States. The most common length of survival following diagnosis is ~12 to 15 months, with fewer than ~3 to 5 percent of people surviving longer than five years.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that present two signals to T cells. Signal #1 is a tumor-specific peptide linked to a major histocompatibility complex (pMHC) to enable selectivity and specificity. Signal #2 is a rationally engineered interleukin 2 (IL-2) molecule to trigger T cell activation. These singular biologics are anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. 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.