NEW YORK – Cambridge, Massachusetts-based Cue Biopharma today announced that it is collaborating with Merck to evaluate its investigational biologic, CUE-101, in combination with Merck's checkpoint inhibitor pembrolizumab (Keytruda) as a first-line therapy for patients with HPV-positive, advanced head and neck cancer.
CUE-101 is a fusion protein that contains a human leukocyte antigen complex, an HPV16 E7 peptide epitope, reduced affinity human interleukin-2 molecules, and an effector attenuated human immunoglobulin G Fc domain. The treatment is designed to induce and expand tumor-specific T cells, specifically, HPV16 E7-specific cytotoxic T cells.
Having entered into the agreement with Merck, Cue Biopharma will conduct a Phase I study, KEYNOTE-A78, to evaluate the combination of CUE-101 and pembrolizumab. The company is simultaneously conducting another Phase I trial evaluating CUE-101 as a monotherapy for patients with recurrent and metastatic head and neck cancers that have progressed following at least one prior systemic therapy.
Data from pre-clinical studies of CUE-101, which were recently published in Clinical Cancer Research, demonstrated induction and expansion of HPV16 E7-specific cytotoxic T cells both as a monotherapy and in combination with an anti-PD1 checkpoint inhibitor. When the therapy was given to mice with HPV16 E7 tumors, the result was a selective expansion of disease-relevant T cells, anti-cancer efficacy, and immunologic memory.
Combining CUE-101 with a checkpoint inhibitor further enhanced its anti-tumor efficacy. According to Cue Biopharma, early data from the first two cohorts of patients given CUE-101 as a monotherapy have demonstrated tolerability and drug exposure, and the company said the results were in line with earlier preclinical findings.
The Phase I trials of both the monotherapy and the pembrolizumab combination are designed to evaluate the safety, tolerability, and mechanism of action for the respective regimens. The study design also incorporates assessment of disease-relevant T cells and additional biomarkers of anti-tumor immune response, as well as exploration of response prediction markers.
"Through the monotherapy and combination studies, we believe we will be able to demonstrate the mechanistic advantages of our approach and platform for modulating disease-relevant T cells directly in the patient's body to safely enhance efficacy over current standards of care," Cue Biopharma CEO Daniel Passeri said in a statement.
The company expects to report initial data from the monotherapy Phase I study in the first half of 2020.