Primary Objectives (parts C&D):
To determine the safety and tolerability of CUE-101 in combination with pembrolizumab [KEYTRUDA® (pembrolizumab) for injection, for IV use] as first-line therapy in HPV16- and HLA-A*0201-positive recurrent and/or metastatic HNSCC patients

To determine the MTD or RP2D of CUE-101 in combination with pembrolizumab [KEYTRUDA® (pembrolizumab) for injection, for IV use] as first-line therapy in HLA-A*0201, HPV16+ recurrent and/or metastatic HNSCC patients

Evaluate the PK of CUE-101 when administered in combination with pembrolizumab in first-line subjects with recurrent/metastatic HPV-driven HNSCC

Secondary Objectives:
To assess the preliminary anticancer activity of CUE-101 in combination with pembrolizumab in HPV16- and HLA-A*0201-positive recurrent and/or metastatic HNSCC patients based on RECIST version 1.1

Assess the potential immunogenicity of CUE-101 (Parts C and D)

Parts C and D The patient population to be enrolled will consist of R/M HLA-A*0201-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.

Inclusion Criteria

  1. ECOG performance status of 0 or 1
  2. Life expectancy ≥12 weeks
  3. Measurable disease as per RECIST 1.1 and documented by CT and/or MRI by the local site investigator/radiology.
  4. All tumors must have histologically or cytologically confirmed diagnoses of recurrent and/or metastatic HNSCC.
  5. Patient must have HLA A*0201 genotype as determined by genomic testing performed at a central laboratory designated by the Sponsor prior to enrollment.
  6. 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.
  7. Patient must have tumor expression of PD L1 (CPS ≥1) as determined by an FDA-approved test.
  8. Acceptable laboratory parameters as follows:
    1. Platelet count ≥100 × 103/μL
    2. Hemoglobin ≥9.0 g/dL.
    3. 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
    4. ALT or AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
    5. Total bilirubin ≤1.5 × ULNCreatinine ≤1.5 mg/dL, or a calculated or measured creatinine clearance ≥30 mL/min.
    6. 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.
  9. 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:
    1. Not a woman of childbearing potential (WOCBP)
    2. 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.

Exclusion Criteria

  1. Patients who have received prior therapy for R/M disease.
  2. Patients with symptomatic CNS metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
    1. Need for concurrent treatment for the CNS disease;
    2. Progression of CNS metastases on MRI or CT for at least 28 days after last day of prior therapy for the CNS metastases.
    3. and/or concurrent leptomeningeal disease or cord compression.
  3. Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed.
  4. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
  5. 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.
  6. Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration.
  7. 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.
  8. Other inclusion/exclusion criteria are present.  Please contact the study team for a complete list.
Clinical Program: Head and Neck Cancer Program
Primary Sponsor: Cue BioPharma, Inc.
Contact Info: 202-994-1179