Actively Recruiting
A Pilot Study of CUE-101 in Combination With Pembrolizumab in Subjects With Newly Diagnosed, Locally Advanced HPV-16 Associated Head and Neck Cancer
Led by Yale University · Updated on 2026-05-13
30
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
Y
Yale University
Lead Sponsor
C
Cue Biopharma
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, and effectiveness of CUE-101 alone and combined with pembrolizumab as neoadjuvant treatments in people with newly diagnosed, locally advanced HPV-16 positive head and neck squamous cell carcinoma who have not received prior treatment. This phase 2, randomized, open-label pilot study focuses on participants who are HLA-A*0201 positive and treatment naive, aiming to improve outcomes before surgery. The study randomly assigns participants to one of three groups: CUE-101 monotherapy, pembrolizumab monotherapy, or a combination of both drugs given sequentially. CUE-101 is given intravenously at 4 mg/kg on Days 1 and 21, while pembrolizumab is administered intravenously at 200 mg on the same days. After completing the neoadjuvant therapy, all participants undergo definitive surgical removal of their tumor. Participants will attend visits for treatment, assessments, and surgery. Researchers will collect blood samples to measure HPV-16 specific CD8+ T cells and evaluate safety and side effects within 30 days of treatment. They will also assess tumor response using pathology and imaging before surgery. The overall study involves monitoring treatment effects, tolerability, and immune response to better understand these therapies in this patient group.
CONDITIONS
Brief Title
CUE-101with Pembrolizumab for Locally Advanced HPV+HNSCCs
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must have a new diagnosis of locally advanced, non-metastatic head and neck squamous cell carcinoma of the oropharynx
- Participants deemed unresectable by a head and neck surgeon due to surgical or tumor-related reasons
- Participants with partial surgical resection and gross residual disease requiring additional treatment
- Tumor must be HPV-16 positive and express p16INK4A confirmed by specific tissue testing
- Tumor tissue must be available for PD-L1 staining and scored for CPS
- Participants must have HLA-A*0201 genotype confirmed by genomic testing
- Must have measurable disease with lesion size criteria as defined
- Age 18 years or older
- ECOG performance status 0 or 1
- Adequate organ and marrow function
- HIV-infected participants must have undetectable viral load on therapy
- Participants with HBV must have undetectable viral load on suppressive therapy
- Participants with HCV must be treated and cured or have undetectable viral load if on treatment
- Participants with prior or concurrent malignancy allowed if not interfering with study assessments
- Cardiac function assessment with NYHA classification class 2B or better
- Male participants must agree to effective contraception during and 120 days after treatment
- Female participants must not be pregnant or breastfeeding and meet contraception requirements
- Ability to understand and sign informed consent
You will not qualify if you...
- Presence of distant or central nervous system metastases or carcinomatous meningitis
- Positive pregnancy test within 72 hours prior to first dose
- Prior radiotherapy or systemic anticancer therapy for the cancer under study
- Participation in another investigational study or device use within 4 weeks prior to first dose
- History of allergic reactions to similar compounds or excipients in study drugs
- History of autoimmune disease except specified exceptions (vitiligo, resolved atopic dermatitis, certain psoriasis, euthyroid Grave's disease)
- History of allogeneic bone marrow, stem-cell, or solid organ transplantation
- Treatment with corticosteroids over 10 mg prednisone or immunosuppressants within 7 days prior to first dose
- Clinically significant cardiovascular disease including recent myocardial infarction, arrhythmias, uncontrolled hypertension, thrombotic events, QTc prolongation, heart failure class III-IV, pericarditis, or myocarditis
- Clinically significant pulmonary compromise
- Significant gastrointestinal disorders including recent perforation, bleeding, pancreatitis, or diverticulitis
- Active infections requiring parenteral treatment within 7 days prior to treatment
- Second primary invasive malignancy not in remission over 2 years except specified exceptions
- Recent trauma or major surgery within 4 weeks prior to first dose
- Receipt of live vaccine within 30 days prior to first dose
- Grade over 2 audiometric hearing loss, neuropathy, or bleeding due to malignancy
- History or current pneumonitis requiring steroids
- Active or recent substance abuse within 1 year prior to treatment
- Uncontrolled intercurrent illness
- Psychiatric or social situations limiting study compliance
- Conditions or abnormalities confounding study results or participation
- Investigative site personnel affiliated with the study
- Prisoners or involuntarily detained individuals
- Pregnant or breastfeeding women
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 21 days
Participants receive neoadjuvant therapy with either CUE-101, pembrolizumab, or a combination of both before surgery.
2 infusion visits on Day 1 and Day 21
Duration - Up to 30 days
Participants undergo definitive surgical resection followed by safety and response assessments.
1 surgery visit and follow-up visits as needed
Trial Site Locations
Total: 1 location
1
Yale University
New Haven, Connecticut, United States, 06510
Actively Recruiting
Research Team
S
Sara Pai
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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