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Head and Neck CancerPhase 1NCT03978689

A Phase 1 Study in Patients With HPV16+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 1 study testing CUE-101 and KEYTRUDA®, Pembrolizumab in people with Head and Neck Cancer and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Cue Biopharma at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multi-center, open-label, phase 1 dose escalation and expansion study evaluating the safety, anti-tumor effect, and immunogenicity of CUE-101 as monotherapy treatment in second line or CUE-101 Combination Therapy with Pembrolizumab in first line patients with HPV16+ Recurrent/Metastatic Head and Neck… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CUE-101 and KEYTRUDA®, Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
17 sitesUnited States
Study dates
30 Jul 2019to 4 Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General:
  • Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease. Patients must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
  • Age ≥18 years old
  • ECOG performance status of 0 or 1
  • Life expectancy ≥12 weeks
  • Measurable disease as per RECIST 1.1 and documented by CT and/or MRI by the local site investigator/radiology. At least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan. Minimum measurement must be >15 mm in the longest diameter by >10 mm in the short axis. Cutaneous or subcutaneous lesions must be measurable by calipers.
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  • Note: Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment.
  • All tumors must have histologically or cytologically confirmed diagnoses of recurrent and/or metastatic HNSCC.
  • Patient must have HLA A*0201 genotype as determined by genomic testing performed at a central laboratory designated by the Sponsor prior to enrollment.
  • Patient must have tumor(s) that are HPV16+ and express 16INK4A. Archival tissue or FFPE tissue from a biopsy and/or surgery must be available for HPV16 and p16INK4A testing on all patients enrolled. All tumors must test positive for both HPV16 using RNA ISH and p16INK4A expression in tumor cells using IHC analysis determined in a central laboratory designated by the Sponsor.
  • Patient must have tumor expression of PD L1 (CPS ≥1) as determined by an FDA-approved test.
  • Laboratory Features
  • Acceptable laboratory parameters as follows:
  • Platelet count ≥100 × 103/μL
  • Hemoglobin ≥9.0 g/dL. Criteria must be met without erythropoietin dependency and without pRBC transfusion within last 2 weeks.
  • Absolute neutrophil count ≥1.5 × 103/μL in the absence of any growth factor support within 2 weeks prior to the initiation of study drug
  • ALT or AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
  • Total bilirubin ≤1.5 × ULN, except patients with Gilbert's syndrome, who may enroll if the conjugated bilirubin (total and direct) is within normal limits
  • Creatinine ≤1.5 mg/dL, or a calculated or measured creatinine clearance ≥30 mL/min. Creatinine clearance should be calculated as per institutional standard. >1.5 x institutional ULN. Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance.
  • Coagulation: INR or PT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range of anticoagulants.
  • Reproductive Features
  • A male participant must agree to use contraception during the treatment period and for at least 120 days following discontinuation of study treatment.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP)
  • A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.

Who cannot join

  • Patients with symptomatic CNS metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
  • Need for concurrent treatment for the CNS disease (eg, surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent);
  • Progression of CNS metastases on MRI or CT for at least 28 days after last day of prior therapy for the CNS metastases; and/or
  • Concurrent leptomeningeal disease or cord compression.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • History of prior allogeneic bone marrow, stem-cell or solid organ transplantation
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  • Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 2 weeks (or 4 weeks, for antibody drugs), prior to the initiation of study drug administration. Patients may be on an investigational or other anti-neoplastic therapy during the screening phase of the study.
  • Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration.
  • Treatment with corticosteroids (>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
  • History of clinically significant cardiovascular disease including, but not limited to:
  • Myocardial infarction or unstable angina within the 16 weeks prior to the initiation of study drug
  • Clinically significant cardiac arrhythmias
  • Uncontrolled HTN: systolic BP >180 mm Hg, diastolic BP >100 mm Hg
  • 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
  • CHF (NY Heart Association Class III IV)
  • Pericarditis/clinically significant pericardial effusion
  • Myocarditis
  • Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen)
  • Clinically significant GI disorders including:
  • History of GI perforation within 1 year prior to study drug administration. Patients with a history of GI perforation that occurred more than 1 year ago can only be enrolled if the 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; and/or
  • Diverticulitis that is clinically significant in the opinion of the investigator based on the extent or severity of known disease and/or the occurrence of clinically significant disease flares within 4 weeks prior to the initiation of study drug administration.
  • Patients who experienced the following immune checkpoint inhibitor-related AEs are ineligible even if the AE resolved to ≤Grade 1 or baseline:
  • ≥Grade 3 ocular AE
  • Changes in liver function tests that met the criteria for Hy's Law (>3 × ULN of either ALT/AST with concurrent >2 × ULN of total bilirubin (total and direct) and without alternate etiology)
  • ≥Grade 3 neurologic toxicity
  • ≥Grade 3 colitis
  • ≥Grade 3 renal toxicity
  • Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients 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.
  • Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
  • Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.
  • 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; 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 the initiation of study drug administration.
  • Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site.
  • Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE 101.
  • Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
  • Dementia or altered mental status that would preclude understanding and rendering of informed consent.
  • Active or history of alcohol or other substance abuse within 1 year prior to the initiation of study drug administration.
  • Any investigative site personnel directly affiliated with this study.
  • Prisoners or other individuals who are involuntarily detained.
  • Any issue that would contraindicate the patient's participation in the study or confound the results of the study.
  • Parts C and D The patient population to be enrolled will consist of R/M HLA-A0201-positive adult patients with HPV-driven HNSCC, as confirmed by tumor HPV16 positivity, expression of p16INK4A and tumor expression of PD L1 (CPS ≥1) as determined by an FDA-approved test, eg, the PD L1 IHC 22C3 pharmDx kit approved for use as a companion diagnostic device.
  • Patients who have received prior therapy for R/M disease.
  • Patients with symptomatic CNS metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
  • Need for concurrent treatment for the CNS disease (eg, surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent);
  • Progression of CNS metastases on MRI or CT for at least 28 days after last day of prior therapy for the CNS metastases. If brain imaging is performed to document the stability of existing metastases, MRI should be used if possible. If MRI is medically contraindicated, CT with contrast is an acceptable alternative.
  • and/or concurrent leptomeningeal disease or cord compression.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • History of prior allogeneic bone marrow, stem-cell or solid organ transplantation
  • Treatment with prior systemic anti-cancer therapy including investigational agents within 4 weeks for antibodies or 5 half-lives for other therapies, whichever is shorter, prior to administration of the study drug. Patients may be on an investigational or other anti-neoplastic therapy during the screening phase of the study.
  • Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration.
  • Treatment with corticosteroids (>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
  • History of clinically significant cardiovascular disease including, but not limited to:
  • Myocardial infarction or unstable angina within the 16 weeks prior to the initiation of study drug
  • Clinically significant cardiac arrhythmias
  • Uncontrolled HTN: systolic BP >180 mm Hg, diastolic BP >100 mm Hg
  • 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
  • CHF (NY Heart Association Class III-IV)
  • Pericarditis/clinically significant pericardial effusion
  • Myocarditis
  • Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen)
  • Clinically significant GI disorders including:
  • History of GI perforation within 1 year prior to study drug administration. Patients with a history of GI perforation that occurred more than 1 year ago can only be enrolled if the 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; and/or
  • Diverticulitis that is clinically significant in the opinion of the investigator based on the extent or severity of known disease and/or the occurrence of clinically significant disease flares within 4 weeks prior to the initiation of study drug administration.
  • Severe hypersensitivity to pembrolizumab excipients.
  • Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients 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.
  • Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
  • Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.
  • 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; 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 the initiation of study drug administration.
  • Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site.
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE 101.
  • Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
  • Dementia or altered mental status that would preclude understanding and rendering of informed consent.
  • Active or history of alcohol or other substance abuse within 3 months prior to the initiation of study drug administration. Medical marijuana use is not allowed on study.
  • Any investigative site personnel directly affiliated with this study.
  • Prisoners or other individuals who are involuntarily detained.
  • Any issue that would contraindicate the patient's participation in the study or confound the results of the study.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of Michigan

    Ann Arbor, Michigan, 48197

  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 20231

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Affiliated Oncologists, LLC

    Chicago, Illinois, 33612

  • Barbara Karmanos Cancer Center/ Wayne State University School of Medicine

    Detroit, Michigan, 48201

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Vanderbilt-Ingram Cancer Center (VICC)

    Nashville, Tennessee, 37232

  • Yale School of Medicine

    New Haven, Connecticut, 06510

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10017

  • Stanford University Medical Center

    Palo Alto, California, 94305

  • University of Washington School of Medicine

    Seattle, Washington, 98195

  • Washington University

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Arizona

    Tucson, Arizona, 85719

  • George Washington University Cancer Center

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: A Phase1, First-in-Human, Open-Label, Dose Escalation and Expansion Study of CUE-101 Monotherapy in Second Line or CUE-101 Combination Therapy With Pembrolizumab in First Line Patients With HPV16+ Recurrent/Metastatic HNSCC

This is a multi-center, open-label, phase 1 dose escalation and expansion study evaluating the safety, anti-tumor effect, and immunogenicity of CUE-101 as monotherapy treatment in second line or CUE-101 Combination Therapy with Pembrolizumab in first line patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Read the detailed description

CUE-101 is a novel fusion protein designed to activate and expand a population of tumor specific T cells to eradicate human papilloma virus (HPV)-driven malignancies. HPV causes multiple tumor types including cervical, head and neck squamous cell carcinoma (HNSCC) and anal cancers. Initial testing of CUE-101 will be conducted in HPV16+ HNSCC patients.

The primary objectives of the Part A\&B, first-in-human trial, are to assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HNSCC in the second line setting and to determine the maximum tolerated dose or recommended Phase 2 dose based on markers of biological activity. Pharmacokinetics (PK), antitumor immune response, preliminary antitumor activity and the potential for immunogenicity will also be assessed. The goal of Part C\&D is to characterize the safety, tolerability, and biological effects of CUE-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC in the first line setting. This will be an open-label multicenter phase I trial conducted in the U.S. involving approximately 85 patients.

Being tested
CUE-101, KEYTRUDA®, Pembrolizumab
Keywords
KEYNOTE' KN-A78
Medical subject headings
Head and Neck Neoplasms

What participants receive

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

  • CUE-101Drug

    CUE-101 is a novel biologic to treat HPV - driven recurrent / metastatic head and neck cancer given as monotherapy in parts A\&B and in combination in Parts C\&D according to the schedule described in the protocol.

  • KEYTRUDA®, PembrolizumabDrug

    Also called Pembrolizumab

    KEYTRUDA® is first-line therapy in HPV16 and HLA A*0201-positive recurrent and/or metastatic HNSCC patients given in combination with CUE-101 in Parts C\&D according to the schedule described in the protocol.

Study groups in NCT03978689
Study groupRoleWhat they receive
CUE-101 dose escalation and expansionExperimentalPart A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)
Receives: Drug: CUE-101
Pembrolizumab and CUE-101OtherPart C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)
Receives: Drug: CUE-101; Drug: KEYTRUDA®, Pembrolizumab

What is being measured

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

  1. Dose Limiting Toxicity

    The number of subjects who have dose limiting toxicities (DLTs), defined as clinically significant or ≥ Grade 3 Common Terminology Criteria for Adverse Events (CTCAE) v5.0, changes in adverse events (AEs), safety laboratory tests, physical examinations, electrocardiograms (ECGs), or vital signs

    Measured: 36 months

  2. Serum PK parameters for CUE-101

    Area under the concentration-time curve (AUC) of CUE-101

    Measured: 36 months

  3. Serum PK parameters for CUE-101

    Maximum serum concentration (Cmax) of CUE-101

    Measured: 36 months

  4. Serum PK parameters for CUE-101

    Terminal half-life of CUE-101

    Measured: 36 months

Secondary outcomes (1)

  1. Overall response rate (ORR)

    For ORR: Complete and partial responses as well as stable disease parameters will be followed

    Measured: 36 months

Timeline

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

  1. First posted7 Jun 2019
  2. Study start30 Jul 2019
  3. Primary completion4 Jan 2026
  4. Study completion4 Jan 2026

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Phase I dose escalation and expansion
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03978689
Sponsor's protocol ID
CUE-101-01
Other IDs
MK-3475-A78, KEYNOTE-A78
Status last verified
Jan 2026
First submitted
4 Jun 2019
Last updated
22 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Quayle SN, Girgis N, Thapa DR, Merazga Z, Kemp MM, Histed A, Zhao F, Moreta M, Ruthardt P, Hulot S, Nelson A, Kraemer LD, Beal DR, Witt L, Ryabin J, Soriano J, Haydock M, Spaulding E, Ross JF, Kiener PA, Almo S, Chaparro R, Seidel R, Suri A, Cemerski S, Pienta KJ, Simcox ME. CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies. Clin Cancer Res. 2020 Apr 15;26(8):1953-1964. doi: 10.1158/1078-0432.CCR-19-3354. Epub 2020 Jan 21.

    PubMed 31964784

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CUE-101 and KEYTRUDA®, Pembrolizumab in people with Head and Neck Cancer and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Cue Biopharma at 17 sites 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 25 inclusion and 84 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: finished, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (time frame: 36 months). The study lists 4 primary outcomes in all. 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 NCT03978689, which also lists 1 linked publication.

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 22 Jan 2026.

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