CUE-101with Pembrolizumab for LA-HPV+HNSCCs

NCT07172256 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000036095
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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, unresectable HPV-16 associated head and neck squamous cell carcinoma (HNSCC).

Conditions

Head and Neck Squamous Cell Carcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma; New Diagnosis Tumor; Locally Advanced

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and perioperative/periprocedural

Secondary Outcomes (3)

• Assessment of Safety and Tolerability of CUE-101 Alone and in Combination with Pembrolizumab

  Up to 30 days

• Evaluation of Pathological Response Rate at End of Neoadjuvant Treatment

  At screening and on the day of surgery

• Evaluation of Radiologic Response Rate at End of Neoadjuvant Treatment

  Baseline and perioperative/periprocedural

Study Arms (3)

Neoadjuvant CUE-101

EXPERIMENTAL

Neoadjuvant therapy followed by definitive surgical resection

Drug: CUE-101

Neoadjuvant Pembro

EXPERIMENTAL

Pembrolizumab Neoadjuvant therapy followed by definitive surgical resection

Drug: Pembrolizumab

Neoadjuvant CUE-101 + Pembro

EXPERIMENTAL

CUE-101+Pembrolizumab as neoadjuvant therapy followed by definitive surgical resection

Drug: CUE-101; Drug: Pembrolizumab

Interventions

CUE-101 DRUG

CUE-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

Neoadjuvant CUE-101; Neoadjuvant CUE-101 + Pembro

Pembrolizumab DRUG

Pembrolizumab 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.

Neoadjuvant CUE-101 + Pembro; Neoadjuvant Pembro

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Participants must be deemed unresectable by a head and neck surgeon for one or more of the following reasons:
• 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.
• Participants with newly diagnosed HNSCC who underwent partial surgical resection and have gross residual disease are eligible for the study if additional treatment is required.
• Participant must have a tumor that is HPV-16 positive and express p16INK4A. Archival tissue or formalin fixed, paraffin-embedded (FFPE) tissue from a biopsy and/or surgery must be available for HPV-16 and p16INK4A testing on all participants enrolled. All tumors must test positive for HPV-16 using ISH analysis or using HPV16 specific PCR testing and p16INK4A expression in tumor cells using IHC analysis.
• Archival tissue or formalin fixed, paraffin-embedded (FFPE) tissue from a biopsy and/or surgery must be available for PD-L1 staining. Tumors must be scored for CPS.
• Participants must have HLA-A\*0201 genotype as determined by genomic testing.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) for non-nodal lesions and \> 15mm (\>1.5 cm) for nodal lesions with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam. See section 11 (Measurement of Effect) for the evaluation of measurable disease.
• Age ≥18 years. Since no dosing or adverse event data are currently available on the use of CUE-101 alone or in combination with pembrolizumab in participants \<18 years of age, children are excluded from this study.
• ECOG performance status of 0 or 1 (Karnofsky ≥60%, see Appendix A).
• Participants must have adequate organ and marrow function as defined below in the protocol
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

You may not qualify if:

• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic. composition to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE-101 or pembrolizumab.
• Participants with any history of known or suspected autoimmune disease with the specific exceptions of the following:
• Vitiligo.
• Resolved childhood atopic dermatitis.
• Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years).
• Participants with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
• History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
• Treatment with corticosteroids (\>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 7 days prior to the first dose of study drug administration. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed. Physiological replacement with hydrocortisone up to a maximum dose of 10 mg per day is allowed.
• History of clinically significant cardiovascular disease including:
• Myocardial infarction or unstable angina within the 16 weeks prior to the initiation of study drug.
• Clinically significant cardiac arrhythmias.

Sponsors & Collaborators

• Yale University: lead
• Cue Biopharma: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Sara Pai, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Pai

CONTACT

(203) 836-0406; sara.pai@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 15, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)