Overview

The researchers are doing this study to find out if HB-202/HB-201 is an effective treatment for people with HPV 16-positive head and neck squamous cell cancer (HPV 16+ HNSCC) who have received standard treatment for their disease but then tested positive for HPV 16-related tumor DNA in the blood through a test called NavDx. Participants will have no evidence of cancer on imaging scans (radiographically) or by medical examination (clinically). Past studies have shown that a positive NavDx test strongly suggests the possible presence of microscopic cancer, though we do not know if testing positive will definitely lead to the cancer coming back (recurrence). The NavDx blood test has not been approved by the FDA and is considered investigational.

Eligibility

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of HPV16+ squamous cell carcinoma of the head and neck post standard of care definitive therapy.
  • History of histologically confirmed HPV16+ squamous cell cancer (from in-house or local evaluation by HPV16 RNA in situ hybridization (ISH) or PCR) is required for all patients on study.
  • Detection of HPV16 specific TTMV-HPV DNA via peripheral blood NavDx assay in combination with historically confirmed p16 expression can be used as a surrogate for enrollment and initiation of treatment as per the discretion of site PI whilst histological confirmation with RNA ISH or PCR is in process.
• No clinical or radiographic evidence of persistent or recurrent disease at time of

  evaluation (indeterminate findings are allowed based on discretion of P.I.)

• Positive TTMV-HPV DNA score (HPV16 specific) by NavDx® 3 months or more after definitive therapy for HPV16+ squamous cell carcinoma of the head and neck allows for pre-screen consent for a confirmatory NavDx.
• Definitive therapy includes surgery or chemotherapy/radiation therapeutic paradigms that are aimed at eradicating and curing disease with the goal of no additional therapies being required afterwards. This will include standard of care treatments and IRB-approved, de-escalation treatment protocols and strategies. Enrollment of patients who had de-escalated treatment performed off an IRB-approved protocol/clinical trial will require the approval of the study P.I.
• Male or female patients 18 years of age or older on the day of consent.
• ECOG Performance Status of 0 to 1.
• Adequate hematologic function within 30 days prior to registration, defined as

  follows

  • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 9.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable

• Adequate renal function within 30 days prior to registration, defined as follows:

  °Serum creatinine < 2.0 x upper limit of normal (ULN) or creatinine clearance (CCr) ≥ 30 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

• Adequate hepatic function within 30 days prior to registration, defined as follows:
  • Total bilirubin ≤ 1.5 × ULN (except for unconjugated hyperbilirubinemia or Gilbert's syndrome). Direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN.
  • AST and ALT ≤ 2.5 x the upper limit of normal
  • Albumin ≥ 3 g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless

  participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants.

• Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Female patients are eligible to participate if they are not pregnant, not breastfeeding and at least one of the following conditions applies:
  • Not a woman of childbearing potential
  • A woman of childbearing potential who agrees to use highly effective contraception from signing of the ICF through five months after the last study treatment administration.

        Notes: i) Female of childbearing potential are those who have not been surgically
        sterilized or have not been free from menses for >1 year.
        ii) Highly effective contraception methods include:
          -  Total abstinence.
          -  Male or female sterilization.
          -  Combination of any 2 of the following categories (Categories 1+2, 1+3, or 2+3):
               -  Category 1: Use of oral, injected, or implanted hormonal methods of
                  contraception.
               -  Category 2: Placement of an intrauterine device or intrauterine system.
               -  Category 3: Barrier methods of contraception: condom or occlusive cap (diaphragm
                  or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
          -  A female participant who is of childbearing potential must have a negative serum
             βhuman chorionic gonadotrophin (β-hCG) pregnancy test within 72 hours prior to the
             first administration of study treatment or be surgically/biologically sterile
             (hysterectomy or bilateral oophorectomy) or postmenopausal. Note: Postmenopausal
             females are defined as those who are:
               -  Age > 50 years with amenorrhea for ≥ 12 months.
               -  Age ≤ 50 years with six months of spontaneous amenorrhea and follicle stimulating
                  hormone level within postmenopausal range (> 40 mIU/mL).
          -  Male patients must agree to use contraception and refrain from sperm and egg donation
             from the time period between signing of the ICF and through five months after the last
             dose of study drug
          -  The subject must provide voluntary study-specific informed consent prior to study
             entry.
        Exclusion Criteria:
          -  Patients with radiographically evident or biopsy proven recurrent or metastatic
             squamous cell carcinoma of the head and neck
          -  Patients with simultaneous primary cancers aside from HPV 16+ HNSCC is excluded unless
             otherwise approved by site PI
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for 3 years or if cure rate for the malignancy treated at 5 years is estimated to be
             90% or greater
          -  Prior systemic chemotherapy or immune checkpoint inhibitor therapy for incurable head
             and neck squamous cell carcinoma (drug therapies in the neoadjuvant and/or
             chemoradiation setting is allowed).
          -  Severe, active co-morbidity defined as the following:
               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months
               -  Transmural myocardial infarction within the last 6 months
               -  Acute infection requiring intravenous therapy at the time of registration
               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days of
                  registration
               -  Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defect
          -  Active, known or suspected, autoimmune or inflammatory disorders requiring
             immunosuppressive therapy, with the exception of low dose prednisone (≤ 10 mg or
             equivalent). The following are exceptions to this criterion:
               -  Patients with vitiligo or alopecia.
               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement
               -  Any chronic skin condition that does not require systemic treatment.
          -  Live vaccines within 28 days prior to the first dose of study treatment and while on
             study treatment, unless agreed otherwise between the Sponsor and Investigator.
          -  Herbal remedies with immune-stimulating properties or known to potentially interfere
             with major organ function within 28 days prior to the first dose of study treatment,
             unless agreed otherwise between the Sponsor and Investigator.
          -  Current use of systemic corticosteroids or use of systemic corticosteroids within 4
             weeks of registration (short term corticosteroid pre-medication for CT or MRI based
             contrast allergies [as per institutional guidelines], doses < 10mg prednisone per day
             or the equivalent, inhaled corticosteroids for asthma or COPD or other non-systemic
             steroids such as topical, intranasal, or intra-articular corticosteroids are
             permitted)
          -  Known acquired immunodeficiency syndrome due to untreated/poorly controlled human
             immunodeficiency virus. Other diagnosed immunodeficiency syndromes or disorders will
             require the review and approval of the site P.I. and consultation with Hookipa.
          -  Positive test for hepatitis B surface antigen (HBsAG) or hepatitis C virus antibody
             (antiHCV), indicating acute or chronic infection. Patients who test positive for
             anti-HCV but negative for HCV ribonucleic acid (RNA) are permitted to enroll.
          -  Female patients who are pregnant, breastfeeding, or plan on becoming pregnant during
             the study.
          -  Patients on chronic antiviral medication for any reason.