Clinical Trials /

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer

NCT04630353

Description:

This Window Of Opportunity clinical trial will examine the immunologic effects of the study agent HB-201 in the head and neck or cervical cancer, when administered either by IT injection or by IV route.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Oropharyngeal Undifferentiated Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer
  • Official Title: A Phase 0 Trial of HB-201 for Subjects With Transoral Resectable Human Papillomavirus 16 Positive (HPV 16+) Oropharynx Cancer or With Locally Advanced Cervical Cancer Treated With Chemotherapy and Radiation

Clinical Trial IDs

  • ORG STUDY ID: H-200-002
  • NCT ID: NCT04630353

Conditions

  • HPV 16+ Confirmed Oropharynx Cancer and Cervical Cancer

Interventions

DrugSynonymsArms
HB-201 ITHB-201 Intratumorally on Day 1
HB-201 IVHB-201 Intravenously on Day 1
HB-201 ITHB-201 Intratumorally 7 to 14 days before chemoradiation

Purpose

This Window Of Opportunity clinical trial will examine the immunologic effects of the study agent HB-201 in the head and neck or cervical cancer, when administered either by IT injection or by IV route.

Detailed Description

      The window of opportunity, Study H-200-002, will examine the effects of study agent (HB-201)
      on subjects during the "window" between diagnosis of their cancer and their definitive cancer
      surgery or chemoradiation.

      The study will be a 2-arm study design. In Arm 1, the study will enroll subjects with
      resectable stage I-III human papillomavirus 16 positive (HPV 16+) genotype squamous cell
      cancer of the oropharynx who are candidates for transoral surgery. Participants will receive
      a single dose of the study agent HB-201 prior to transoral surgery. Arm 1 will consist of 2
      Cohort groups; Cohort 1 will enroll subjects receiving HB-201 as an intratumoral injection
      and Cohort 2 will enroll patients receiving HB-201 administered intravenously.

      In Arm 2, the study will enroll cervical cancer subjects who have locally advanced squamous
      cell carcinoma, adenocarcinoma, and/ or adenosquamous cell carcinoma with HPV 16+ genotype.
      Subjects with advanced/metastatic disease that are previously untreated who are planning to
      undergo upfront chemoradiation for local control are eligible and will receive an
      intratumoral injection of HB-201 prior to the start of chemoradiation.
    

Trial Arms

NameTypeDescriptionInterventions
HB-201 Intratumorally on Day 1ExperimentalPatients with resectable stage I-III, HPV 16+ genotype squamous cell cancer of the oropharynx.
  • HB-201 IT
HB-201 Intravenously on Day 1ExperimentalPatients with resectable stage I-III, HPV 16+ genotype squamous cell cancer of the oropharynx.
  • HB-201 IV
HB-201 Intratumorally 7 to 14 days before chemoradiationExperimentalPatients with cervical cancer who have locally advanced squamous cell carcinoma with HPV 16+ genotype.
  • HB-201 IT

Eligibility Criteria

        Inclusion Criteria:

        All subjects:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Confirmed HPV 16+ (human papilloma virus 16 positive) genotype testing of cancer.

          -  Disease-free for ≥ 2 years from other curatively treated cancers, with
             protocol-defined exceptions.

          -  Evaluated by cardiologist and/or neurologist if protocol-defined cardiac or
             neurological event within the last 6 months.

        HPV 16+ Oropharynx Cancer (Arm 1 Cohorts 1 and 2)

          -  Newly diagnosed, squamous cell carcinoma or undifferentiated carcinoma of the
             oropharynx, determined to be resectable.

          -  AJCC v8.0 Tumor, Node, Metastasis (TNM) stage I-III, cT1- T3, and cervical nodes N1-N3
             based on clinical or radiographic criteria with no evidence of distant metastases.

          -  No prior radiation above the clavicles.

          -  Must have acceptable renal and hepatic function as defined per protocol.

          -  Cohort 2 (intratumoral administration) only: must have a safe and accessible tumor
             lesion amenable for biopsy and IT administration.

        HPV 16+ Cervical Cancer (Arm 2)

          -  Newly diagnosed, histologically confirmed advanced cervical cancer (squamous cell
             carcinoma, adenocarcinoma, or adenosquamous cell carcinoma): International Federation
             of Gynecology and Obstetrics (FIGO) clinical stages IB to IVB with plan for initial
             treatment of definitive chemoradiation (platinum agent weekly with radiotherapy) for
             either curative intent or control of local (pelvic) disease.

          -  No prior radiation to the abdomen or pelvis.

          -  Must have a safe and accessible tumor lesion amenable for biopsy and IT
             administration.

          -  Must have normal organ and marrow function as defined per protocol.

          -  Must not have a known allergy to cisplatin, carboplatin, or compounds of similar
             biologic composition.

        Exclusion Criteria:

        All subjects:

          -  Treatment with any systemic anticancer therapy within 3 years (unless agreed otherwise
             between the Sponsor and the Investigator).

          -  Treatment with any chronic immunosuppressive medication within 6 months (unless agreed
             otherwise between the Sponsor and Investigator).

          -  Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled
             hypertension.

          -  Live vaccine within 28 days (unless agreed otherwise between Sponsor and
             Investigator).

          -  Known diagnosis of acquired immunodeficiency syndrome (AIDS).

          -  Positive Hepatitis B or Hepatitis C tests indicating acute or chronic infection.

          -  Intercurrent illness likely to interfere with protocol therapy.

          -  Female subjects who are pregnant or breastfeeding.

          -  Female subjects of childbearing potential who do not agree to the use of highly
             effective contraception per protocol.

          -  Male subjects with sexual partners of childbearing potential who do not agree to the
             use of protocol-defined contraception

        HPV 16+ Oropharynx Cancer (Arm 1 Cohorts 1 and 2)

        • Primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical
        spine.

        HPV 16+ Cervical Cancer (Arm 2)

          -  Treatment with chemotherapy for cervical cancer, prior to planned chemoradiation.

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune response profiles in subjects with HPV 16+ Head and Neck and cervical cancer.
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Measurement of antigen-specific CD8+ T cells in blood and tissue (E7E6 antigen specific assay).

Secondary Outcome Measures

Measure:Measurement of messenger RNA and expression profiles in tumor specimens using RNA-sequencing (800 genes).
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Pre and post administration of HB-201
Measure:Assessment of tumor mutational burden (TMB, MSI) in tumor specimens using whole exome sequencing.
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Pre and post administration of HB-201
Measure:Measure TH1/TH2 proinflammatory cytokines (mesoscale multiplex discovery assay) to characterize metabolic / proteomic changes in serum / plasma
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Pre and post administration of HB-201
Measure:Measure ctDNA to characterize changes in circulating tumor by NextGen sequencing.
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Pre and post administration of HB-201
Measure:Characterize t-cell receptor repertoire diversity and clonality, by t-cell receptor sequencing.
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Pre and post administration of HB-201.
Measure:Clinical evidence of response to HB-201
Time Frame:Approximately 6-8 weeks
Safety Issue:
Description:Change in tumor size per RECIST v1.1
Measure:Toxicity profile of HB-201
Time Frame:Approximately 30 days post HB-201 administration
Safety Issue:
Description:Number and type of adverse events per CTCAE v5.0

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hookipa Biotech GmbH

Trial Keywords

  • HPV
  • Oropharynx Cancer
  • Cervical Cancer
  • Intratumoral
  • Intravenous
  • Lymphocytic Choriomeningitis Virus
  • Medical College of Wisconsin Cancer Center
  • Medical College of Wisconsin
  • Transoral Surgery
  • Window of Opportunity
  • HPV 16+
  • HPV 16+ head and neck squamous cell cancer
  • HPV 16 E7E6
  • E7E6

Last Updated

November 16, 2020