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Head and Neck Squamous Cell CarcinomaPhase 2NCT07172256

CUE-101with Pembrolizumab for Locally Advanced HPV+HNSCCs

A Phase 2 study testing CUE-101 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Yale University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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 HPV-16 associated head and neck squamous… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
CUE-101 and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
7 May 2026to Feb 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • A male participant must agree to use of a highly effective method of contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) as defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal or
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
  • Highly effective methods of contraception:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal.
  • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable.
  • Non-hormonal (copper) intrauterine device. iv. Intrauterine hormone-releasing system. v. Bilateral tubal occlusion/ligation. vi. Sexual abstinence, i.e., refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant).
  • Vasectomized sexual partner (provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success).
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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:
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  • 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.
  • Hashimoto's thyroiditis.
  • 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.
  • Uncontrolled hypertension: systolic blood pressure (BP) > 180 mmHg, diastolic BP >100 mmHg.
  • Deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack within the 16 weeks prior to the initiation of study drug.
  • QTcB prolongation > 480 msec.
  • Congestive heart failure (New York heart Association class III-IV).
  • Pericarditis/clinically significant pericardial effusion.
  • Myocarditis.
  • Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen)
  • Clinically significant GI disorders including:
  • History of GI perforation within 1 year prior to study drug administration. Participants with a history of GI perforation that occurred more than 1 year ago can only be enrolled if the sponsor-investigator no longer considers the previously affected area to be at risk for perforation.
  • History of clinically significant GI bleeding within 3 months prior to the initiation of study drug.
  • History of acute pancreatitis within 3 months prior to the initiation of study drug.
  • Diverticulitis that is clinically significant in the opinion of the sponsor-investigator based on the extent or severity of known disease and/or the occurrence of clinically significant disease flares within four weeks prior to the initiation of study drug administration.
  • Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within seven days prior to the initiation of study drug. Participants requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than 1 week prior to the initiation of study drug
  • Second primary invasive malignancy that has not been in remission for > 2 years. Exceptions that do not require a 2-year remission include: non-melanoma skin cancer; cervical carcinoma in situ on biopsy; or squamous intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score <6); or resected melanoma in situ.
  • History of trauma or major surgery within 4 weeks prior to first dose of study drug.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
  • Has Grade > 2 audiometric hearing loss. Note: Audiometric abnormalities without corresponding clinical symptoms of Grade > 2 hearing loss will not be grounds for exclusion.
  • Has Grade > 2 neuropathy.
  • Has Grade > 2 bleeding due to the underlying malignancy.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Active or history of alcohol or other substance abuse within 1 year prior to the initiation of study drug administration.
  • Participants with uncontrolled intercurrent illness.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements, as determined by the treating investigator.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Any investigative site personnel directly affiliated with this study.
  • Prisoners or other individuals who are involuntarily detained.
  • Pregnant women are excluded from this study because it is unknown whether CUE-101 and/or pembrolizumab is an agent with the potential for teratogenic or abortifacient effects. It is unknown whether pembrolizumab is excreted in human milk. Since many drugs are excreted in human milk, and because of the potential for serious adverse reactions in the nursing infant, participants who are breast feeding are not eligible for enrollment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sara Pai contact

(203) 836-0406

sara.pai@yale.edu

United States1 site, 1 recruiting

  • Yale University

    New Haven, Connecticut, 06510

    Sara Pai, MD, 203-836-0406, Sara.Pai@yale.edu

    Sara Pai, MD

    Recruiting

Other trials in United States

About this study

Official title: A Pilot Study of CUE-101 in Combination With Pembrolizumab in Subjects With Newly Diagnosed, Locally Advanced HPV-16 Associated Head and Neck Cancer

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).

Read the detailed description

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).

CUE-101 monotherapy will be administered at 4 mg/kg IV on Days 1 and 21. Pembrolizumab monotherapy will be administered at 200 mg IV on Days 1 and 21. CUE-101 and pembrolizumab combination therapy will be administered by sequential infusion. Pembrolizumab will be administered at 200 mg IV followed by CUE-101 will be administered at 4 mg/kg IV on Days 1 and 21.

Being tested
CUE-101, Pembrolizumab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CUE-101Drug

    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

  • PembrolizumabDrug

    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.

Study groups in NCT07172256
Study groupRoleWhat they receive
Neoadjuvant CUE-101ExperimentalNeoadjuvant therapy followed by definitive surgical resection
Receives: Drug: CUE-101
Neoadjuvant PembroExperimentalPembrolizumab Neoadjuvant therapy followed by definitive surgical resection
Receives: Drug: Pembrolizumab
Neoadjuvant CUE-101 + PembroExperimentalCUE-101+Pembrolizumab as neoadjuvant therapy followed by definitive surgical resection
Receives: Drug: CUE-101; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and perioperative/periprocedural

Secondary outcomes (3)

  1. 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.

    Measured: Up to 30 days

  2. 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.

    Measured: At screening and on the day of surgery

  3. 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.

    Measured: Baseline and perioperative/periprocedural

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2025
  2. Study start7 May 2026
  3. Primary completionFeb 2031 (estimated)
  4. Study completionFeb 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07172256
Sponsor's protocol ID
2000036095
Status last verified
Jul 2026
First submitted
3 Sep 2025
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CUE-101 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sara Pai ((203) 836-0406, sara.pai@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of HPV-16 E711-20-Specific CD8+ T Cells in Peripheral Blood (time frame: Baseline and perioperative/periprocedural). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07172256.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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