Cue Biopharma Announces New Complete Response and 50% Confirmed ORR In Phase 1 Study Of CUE-101 In Combination With Pembrolizumab For Recurrent/Metastatic HPV-Positive Head And Neck Cancer

Cue Biopharma, Inc., a clinical-stage biopharmaceutical company developing targeted biologics to modulate disease-specific T cells for treating autoimmune diseases and cancer, has shared a clinical update on its lead candidate, CUE-101, part of the CUE-100 series. The update focuses on data from the expansion phase of the ongoing trial evaluating CUE-101 at the recommended Phase 2 dose of 4 mg/kg in combination with pembrolizumab for first-line (1L) treatment in patients with head and neck cancer. 

As of the data cutoff on July 14, 2025, the combination therapy showed an objective response rate (ORR) of 50%, including two complete responses and ten partial responses in patients with a combined positive score (CPS) of 1 or higher. This is more than double the 19% ORR reported for pembrolizumab alone in the historical KEYNOTE-048 trial.

Matteo Levisetti, chief medical officer at Cue Biopharma, stated, “We are excited to report an additional CR in a patient that had recurrent metastatic HPV+ head and neck squamous cell carcinoma (HNSCC) treated with CUE-101 in combination with pembrolizumab (KEYTRUDA®). This patient had durable stable disease for close to two years and more recently demonstrated significant tumor reductions and now a complete response. Notably, the patient had multiple sites of disease, including the lungs that cleared prior to the complete response observed in the target lesion.”

He further added, “We believe the kinetics of tumor reduction and disease eradication in this patient is due to the repeated stimulation and expansion of tumor-specific T cells given the mechanism of action of CUE-101. It also serves as a clear example of the differences in timing of the clinical activity often observed with immunotherapy compared to traditional cytotoxic therapies and supports the prolonged mOS observed in this trial.”

Dan Passeri, Chief Executive Officer at Cue Biopharma, mentioned, "The culmination of maturing data further supports our conviction that CUE-101, representative of our approach with the CUE-100 series, demonstrates a potential breakthrough therapeutic approach for establishing a new standard of care. With this maturing data, we are further emboldened in our conviction that our Immuno-STAT® platform represents transformative potential for selectively modulating the patient’s immune system.”

The combination also showed promising survival outcomes. The 12-month overall survival (OS) rate was 88%, compared to 57% with pembrolizumab alone in the same historical trial, translating to a reduced risk of death with a hazard ratio (HR) of 0.23. Median overall survival (mOS) reached 32 months with the CUE-101 combination, compared to 12.3 months historically with pembrolizumab monotherapy. Additionally, the ORR remained consistent at 50% even in patients with lower PD-L1 expression (CPS 1–19), suggesting the treatment’s potential effectiveness across a broader patient population.