The U.S. Food and Drug Administration (FDA) has accepted Cue Biopharma‘s investigational new drug (IND) application for its immunotherapy candidate CUE-101, clearing the way for the first-in-human Phase 1 trial in people with head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus (HPV).
CUE-101 is an immuno-oncology biologic therapy that is based on Cue’s proprietary platform immuno-STAT, which causes the selective targeting and alteration of T-cells. This novel therapy was specifically designed to activate and expand a population of anti-cancer-specific T-cells to fight HPV-driven tumors.
It combines an IL-2 signaling molecule — a potent activator of immune cells — with a fragment of E7 protein, which is carried by malignant types of HPV. This particular cocktail is expected to boost anti-tumor, E7-driven T-cell responses without the typical side effects associated with many immunotherapies, which can affect immune cells other than just T-cells.
In preclinical studies, CUE-101 showed it could selectively bind to T-cells, and aid in the activation and expansion of E7-specific targeting cells. It also demonstrated the potential to stop tumor growth when used as a single therapy, and also in combination with a PD-1 inhibitor.
Encouraged by these results, Cue Biopharma filed an IND to push the therapy forward to clinical studies in people, which was now cleared by the FDA.
“The ability to offer a therapeutic with the potential to activate and amplify cancer-specific T cells directly in a patient’s body differentiates CUE-101 from other immunotherapies in development,” Ken Pienta, MD, chief medical officer of Cue Biopharma, said in a press release. “We are pleased to enter the clinic with CUE-101 and provide patients suffering from HPV-driven cancers with this promising new clinical drug candidate.”
The first planned trial will be an open-label, multi-center Phase 1 study aimed at assessing the safety and tolerability of CUE-101 in people with recurrent or metastatic (spread) HNSCC — a type of cancer that can be caused by HPV.
Researchers will determine the maximum tolerated dose, and establish the recommended dose of CUE-101 to be used in future Phase 2 studies, based on markers of biological activity. Other trial aims including measuring the therapy’s pharmacokinetics — its absorption and distribution in the body — anti-tumor immune response, and preliminary anti-tumor effectiveness.
This trial will be conducted in the U.S. and is expected to enroll approximately 50 patients.
“Our clinical trial of CUE-101 aims to replicate promising pre-clinical studies that have shown the ability to expand specific T cell populations exhibiting polyfunctionality, which is characteristic of potent anti-tumor activity,” said Dan Passeri, president and CEO of Cue Biopharma. “We believe CUE-101 will enhance anti-tumor immunity in patients with HPV 16-driven malignancies.”
With the IND acceptance, Cue Biopharma earned $2.5 million from LG Chem Life Sciences, the life sciences division of LG Chem Ltd.. The milestone payment was part of the companies’ licensing agreement to develop multiple Immuno-STAT biologics in the field of oncology.
HPV cancers lead to over 20,000 deaths each year in the U.S. and Europe, mostly due to HPV 16. Approximately 50% of patients with advanced disease will see their cancer come back after standard treatment. People with HPV-related head and neck, cervical, and genitoanal cancers “represent an important unmet clinical need and underscore the opportunity for promising new therapeutics,” the company said.