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

NCT03978689 | Completed Phase 1 FDA Drug

• 3 other identifiers: CUE-101-01MK-3475-A78KEYNOTE-A78
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 17

Brief 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 Squamous Cell Carcinoma (HNSCC)

Conditions

HPV-Related Carcinoma; Head and Neck Cancer; HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

KEYNOTE' KN-A78

Outcome Measures

Primary Outcomes (4)

• 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

  36 months

• Serum PK parameters for CUE-101

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

  36 months

• Serum PK parameters for CUE-101

  Maximum serum concentration (Cmax) of CUE-101

  36 months

• Serum PK parameters for CUE-101

  Terminal half-life of CUE-101

  36 months

Secondary Outcomes (1)

• Overall response rate (ORR)

  36 months

Study Arms (2)

CUE-101 dose escalation and expansion

EXPERIMENTAL

Part A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)

Drug: CUE-101

Pembrolizumab and CUE-101

OTHER

Part 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)

Drug: CUE-101; Drug: KEYTRUDA®, Pembrolizumab

Interventions

CUE-101 DRUG

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.

CUE-101 dose escalation and expansion; Pembrolizumab and CUE-101

KEYTRUDA®, Pembrolizumab DRUG

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.

Also known as: Pembrolizumab

Pembrolizumab and CUE-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Cue Biopharma: lead

Study Sites (17)

University of Arizona

Tucson, Arizona, 85719, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

George Washington University Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Affiliated Oncologists, LLC

Chicago, Illinois, 33612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 20231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48197, United States

Location

Barbara Karmanos Cancer Center/ Wayne State University School of Medicine

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10017, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Vanderbilt-Ingram Cancer Center (VICC)

Nashville, Tennessee, 37232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• 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.

  PMID: 31964784 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Matteo Levisetti, MD

  Cue Biopharma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I dose escalation and expansion

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 7, 2019
• Study Start: July 30, 2019
• Primary Completion: January 4, 2026
• Study Completion: January 4, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (17)