FDA Grants Fast Track Designation to CUE-101 ± Pembrolizumab for HPV16+ Advanced HNSCC


CUE-101 alone or in combination with pembrolizumab was granted fast track designation by the FDA for patients with human papillomavirus 16–positive recurrent/metastatic head and neck squamous cell carcinoma.

CUE-101 has been granted fast track designation by the FDA both as a single agent and in combination with pembrolizumab (Keytruda) for patients with human papillomavirus 16–positive (HPV16) recurrent/metastatic head and neck squamous cell carcinoma, according to a press release from Cue Biopharma.

A phase 1b dose escalation/expansion trial (NCT03978689) is underway evaluating CUE-101 as a monotherapy, as well as in combination with pembrolizumab, in the aforementioned patient population.

CUE-101 is an interleukin-2 (IL2)–based biologic that activates and expands HPV16–based tumor-specific T cells through 2 signals. The first uses the HPV E7 protein, providing selectivity through HPV-specific T-cell receptors. The second signal includes the IL-2 variant and stimulates the activity of T cells.

“We are very pleased to have received fast track designation from the FDA for CUE-101. This designation not only underscores the large unmet need for patients with [recurrent/metastatic] head and neck cancer who currently rely on available non-targeted therapies but also highlights the potential of CUE-101 to provide a significant clinical benefit,” Matteo Levisetti, MD, senior vice president of Clinical Development at Cue Biopharma, said in the press release.

The non-randomized, first-in-human, open-label study has an estimated enrollment of 85 patients. Patients will receive either CUE-101 monotherapy intravenously every 3 weeks, or 200 mg of CUE-101 plus pembrolizumab intravenously at every 3 weeks.

The primary end points were dose-limiting toxicities, and serum pharmacokinetics parameters for CUE-101 which included the area under the curve concentration time, maximum serum concentration, and the terminal half-life. The secondary end point was overall response rate at 36 months.

Patients were eligible for treatment if they had an ECOG performance status of 0 or 1, a life expectancy of 12 weeks or more, measurable and documented disease, and disease that has progressed after at least 1 prior systemic therapy. Patients must also have an HLA A*0201 genotype determined via genetic testing, histologically and/or cytologically confirmed disease, and acceptable laboratory parameters.

Exclusion criteria included having symptomatic central nervous system metastases, an active autoimmune disease, prior allogeneic bone marrow transplant, or treatment with any systemic anti-neoplastic therapy. Additionally, patients must not have received radiation within 2 weeks prior to the initiation of the study drug, treatment with corticosteroids, or a history of cardiovascular disease. Of note, those with pulmonary compromise; gastrointestinal disorders; active viral, bacteria, or systemic fungal infection; or positive testing for human immunodeficiency virus or history or acquired immune deficiency syndrome were also excluded.

“To date in its phase 1b clinical trials, CUE-101 has demonstrated a favorable tolerability profile and single-agent anti-tumor activity in monotherapy as well as encouraging anti-tumor clinical activity in combination with pembrolizumab, supporting the potential to improve overall survival for these patients. We look forward to providing periodic updates and remain committed to advancing the development of CUE-101 to provide patients with a potentially more effective and better-tolerated treatment option. We anticipate initiating a registrational trial for CUE-101 monotherapy by mid-2023,” Levisetti concluded.


Cue Biopharma granted FDA fast track designation for CUE-101 for the treatment of recurrent/metastatic head and neck squamous cell carcinoma. News Release. Cue Biopharma. October 4, 2022. Accessed October 4, 2022. https://bit.ly/3SCsChQ

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