This is a phase 2, pilot, randomized, open-label 3-arm study to assess the safety, tolerability, and efficacy of CUE-101 monotherapy, and CUE-101 in combination with pembrolizumab as neoadjuvant therapy in HLA-A\*0201-positive treatment naive participants with locally advanced HPV-16 associated head and neck squamous cell carcinoma (HNSCC).
Participants must have histologically or cytologically confirmed new diagnosis of locally advanced, non-metastatic, head and neck squamous cell carcinoma of the oropharynx (cT1-4 N0-N3 M0)
Inability to obtain a R0 resection with a minimally invasive surgical approach, such as Transoral Robotic Surgery (TORS)
Risk of significant functional deficit with a surgical treatment approach
Other anatomical (such as retropharyngeal location of the carotid artery) or tumor characteristics that in the surgeon's judgment would be a contra-indication to a minimally invasive surgical approach.
Has distant metastases or radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Participants who received prior radiotherapy treatment or systemic anticancer therapy including any other investigational agents for the HNC under study prior to first dose of study drug.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug.
Parallel
CUE-101
DrugCUE-101 will be administered by IV infusion with a commercially available syringe pump or IV infusion pump over 60 minutes on Day 1 and Day 21 after all procedures and assessments are completed. It will be administered at a dosage level of 4 mg/kg x 2
Pembrolizumab
DrugPembrolizumab will be administered on Day 1 and Day 21 after all procedures and assessments are completed according to the Study Calendar. Pembrolizumab will be administered as a dose of 200 mg using a 30-minute (- 5 min/+10 min) IV infusion.
Measurement of HPV-16 E711-20-Specific CD8+ T Cells in Peripheral Blood
This outcome measure evaluates the immune response by quantifying the presence of HPV-16 E711-20-specific CD8+ T cells in the peripheral blood at the conclusion of neoadjuvant treatment. The assessment will involve collecting blood samples from participants and analyzing them for the presence and quantity of these specific CD8+ T cells using immunological assays. The primary endpoint is the change in the number of HPV-16 E711-20-specific CD8+ T cells from baseline to the end of the treatment period.
Assessment of Safety and Tolerability of CUE-101 Alone and in Combination with Pembrolizumab
This secondary outcome measure evaluates the safety and tolerability of CUE-101, both as a monotherapy and in combination with pembrolizumab, in the neoadjuvant setting. Safety assessments will include monitoring and recording adverse events, serious adverse events, and any dose-limiting toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Additionally, tolerability will be assessed through patient-reported outcomes and clinical observations. The study will record and analyze the frequency, severity, and relationship of adverse events to the study treatments over the course of the treatment period. The secondary endpoint is to determine the incidence, nature, and duration of adverse events, and to provide an overall tolerability profile of the therapeutic regimens.
Evaluation of Pathological Response Rate at End of Neoadjuvant Treatment
This secondary outcome measure aims to evaluate the rate of pathological response in participants who undergo subsequent resection after completing neoadjuvant treatment. Pathological response will be assessed by examining resected tumor samples post-treatment to determine the extent of cancer cell death and tumor regression. The assessment criteria will include standardized histopathological evaluation methods to classify the degree of response, ranging from complete pathological response (no residual tumor) to partial or minimal response. The secondary endpoint is the proportion of participants achieving each defined level of pathological response at the time of surgery, providing insight into the effectiveness of the neoadjuvant treatment in inducing tumor regression.
Evaluation of Radiologic Response Rate at End of Neoadjuvant Treatment
This secondary outcome measure aims to evaluate the radiologic response rate among participants at the conclusion of neoadjuvant treatment. Radiologic response will be assessed using imaging studies, CT/MRI head and neck, chest and upper abdomen, conducted before and after the treatment period. The response will be evaluated according to standardized criteria, such as the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, to classify the degree of tumor size reduction and overall response to treatment. The secondary endpoint is the proportion of participants achieving each defined level of radiologic response (complete response, partial response, stable disease, or progressive disease) at the end of the neoadjuvant treatment period. This evaluation will provide important insights into the effectiveness of the neoadjuvant therapy in reducing tumor burden as evidenced by imaging studies.
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