Clinical Trials /

A Study of TheraT® Vector(s) Expressing HPV 16+ in Patients With HPV 16+ Confirmed Cancers

NCT04180215

Description:

This is an First in Human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 single vector therapy and HB-201 & HB-202 two-vector therapy in patients with HPV 16+ confirmed cancers comprising two parts: Phase I Dose Escalation and Phase II Dose Expansion.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of TheraT® Vector(s) Expressing HPV 16+ in Patients With HPV 16+ Confirmed Cancers
  • Official Title: A Phase I/II Study of TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV 16+) Specific Antigens in Patients With HPV 16+ Confirmed Cancers

Clinical Trial IDs

  • ORG STUDY ID: H-200-001
  • SECONDARY ID: 2019-000907-34
  • NCT ID: NCT04180215

Conditions

  • HPV-Related Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
HB-201 intravenous administrationPh I, Group 1 HB-201 IV only
HB-201 intratumoral administration on first cycle, followed by HB-201 intravenous administration on subsequent cyclesPh I, Group 2 HB-201 IT-IV
HB-202 intravenous administration alternating with HB-201 intravenous administrationPh I, Group 3 HB-202 IV + HB-201 IV
HB-201 intratumoral administration on first cycle, followed by HB-202 intravenous administration alternating with HB-201 intravenousPh I, Group 4 HB-201 IT, followed by HB-202 IV + HB-201 IV
HB-201 intravenous administration + nivolumabPh II, Group B HB-201 IV only + nivolumab
Alternating HB-202 IV and HB-201 IVPh II, Group D with alternating HB-202 IV and HB-201 IV
HB-202 IV and HB-201 IV + nivolumabPh II, Group E HB-202 IV and HB-201 IV + nivolumab
HB-201 IT & alternating HB-202 IV & HB-201 IVPh II, Group F HB-201 IT & alternating HB-202 IV & HB-201 IV

Purpose

This is an First in Human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 monotherapy and HB-201 & HB-202 combination therapy in patients with HPV 16+ confirmed cancers comprising two parts: Phase I Dose Escalation and Phase II Dose Expansion.

Detailed Description

      The Phase I Dose Escalation will comprise two treatment groups (Groups 1 and 2) of HB-201
      monotherapy and two treatment groups (Groups 3 and 4) of HB-201 & HB-202 dual drug regimen.
      Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose
      (RP2D) of HB- 201 for intravenous (IV) and intratumoral (IT) treatment. Group 3 and Group 4
      Phase I Dose Escalation will determine a safe RP2D of HB-202 for IV.

      The Phase II Dose Expansion may have up to six treatment groups (Groups A to F). Groups A
      will consist of HB-201 monotherapy administered IV , Group B will consist of HB-201
      monotherapy administered IV in combination with an immune checkpoint inhibitor ; Group C will
      consist of HB-201 monotherapy as an IT administration for the first dose, followed by HB-201
      monotherapy as an IV administration; Group D will be Sequential and alternating
      administrations of HB-202 IV and HB-201 IV; Group E will be sequential and alternating
      administrations of HB-202 IV and HB-201 IV with an immune checkpoint inhibitor; Group F will
      be the administration of HB-201 monotherapy IT for the first dose, followed by a sequential
      alternating administration of HB-202 IV and HB-201 IV.
    

Trial Arms

NameTypeDescriptionInterventions
Ph I, Group 1 HB-201 IV onlyExperimentalHB-201 as an IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • HB-201 intravenous administration
Ph I, Group 2 HB-201 IT-IVExperimentalHB-201 as an IT administration for the first dose, followed by HB-201 as an IV administration for the subsequent doses in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • HB-201 intratumoral administration on first cycle, followed by HB-201 intravenous administration on subsequent cycles
Ph I, Group 3 HB-202 IV + HB-201 IVExperimentalHB-202 as an IV administration (initial) and then alternating with HB-201 IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • HB-202 intravenous administration alternating with HB-201 intravenous administration
Ph I, Group 4 HB-201 IT, followed by HB-202 IV + HB-201 IVExperimentalHB-201 as an IT administration for the first dose, and then alternating with HB-202 IV and HB-201 IV administration each cycle in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • HB-201 intratumoral administration on first cycle, followed by HB-202 intravenous administration alternating with HB-201 intravenous
Ph II, Group A-HB-201 IV onlyExperimentalHB-201 as an IV administration in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • HB-201 intravenous administration
Ph II, Group B HB-201 IV only + nivolumabExperimentalHB-201 administered IV with nivolumab in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive nivolumab.
  • HB-201 intravenous administration + nivolumab
Ph II, Group C HB-201 IT-IVExperimentalHB-201 as an IT administration for the first dose, followed by HB 201 as an IV administration for the subsequent doses in patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • HB-201 intratumoral administration on first cycle, followed by HB-201 intravenous administration on subsequent cycles
Ph II, Group D with alternating HB-202 IV and HB-201 IVExperimentalSequential alternating administrations of HB 202 IV and HB 201 IV in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
  • Alternating HB-202 IV and HB-201 IV
Ph II, Group E HB-202 IV and HB-201 IV + nivolumabExperimentalSequential alternating administrations of HB-202 IV and HB-201 IV, and nivolumab in patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy and are eligible to receive nivolumab.
  • HB-202 IV and HB-201 IV + nivolumab
Ph II, Group F HB-201 IT & alternating HB-202 IV & HB-201 IVExperimentalAdministration of HB-201 IT for the first dose, followed by sequential alternating administrations of HB-202 IV and HB-201 IV patients with HPV 16+ cancers with a safe and accessible tumor site amenable for IT administration who had tumor progression or recurrence on standard of care therapy.
  • HB-201 IT & alternating HB-202 IV & HB-201 IV

Eligibility Criteria

        Inclusion Criteria

        All Patients:

          1. Male or female patients 18 years of age, or older, at the time of signing the Informed
             Consent Form (ICF).

          2. Patient must have ≥ 1 measurable lesion by computed tomography (CT) and/or magnetic
             resonance imaging (MRI), that will be assessed for tumor response following RECIST and
             immune Response Evaluation Criteria in Solid Tumors (iRECIST) during study conduct.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          4. Prior curative radiation therapy must have been completed ≥ 4 weeks prior to study
             treatment administration. Prior focal palliative radiotherapy must have been completed
             ≥ 2 weeks prior to study treatment administration.

          5. Screening laboratory values must meet the following criteria and should be obtained
             within 28 days prior to study treatment administration.

          6. Able to understand and willing to comply with study procedures, restrictions, and
             requirements, in the opinion of the Investigator.

          7. Willing and able to give voluntary informed consent for participation in the study.

             Treatment Group 1, Group 3, Group A, or Group D

          8. Patient must have documentation of confirmed HPV 16+ HNSCC via genotype testing as
             specified.

          9. Patient must have had tumor progression or recurrence on standard of care therapy,
             including ≥ 1 systemic therapy, (e.g., failed platinum-based therapy and/or PD L1
             therapy) or be a patient for whom standard of care therapy is contraindicated.

         10. Tumor tissue (archival [no older than two years] or able to provide fresh biopsy
             specimen during Screening) collected following the patient's progression from the last
             treatment,unless agreed otherwise between the Sponsor and the Investigator.

             Treatment Group 2, Group 4, Group C, or Group F, if IT administration of the dose
             level explored is not feasible

         11. Documentation of confirmed HPV 16+ cancer (of any origin) via genotype testing as
             specified.

         12. Patients who have had tumor progression or recurrence on standard of care therapy,
             including ≥ 1 systemic therapy, or for patients for whom standard of care therapy is
             contraindicated.

         13. Patient must have a safe and accessible tumor site amenable for biopsy and IT
             administration, unless agreed otherwise between the Sponsor and the Investigator.

         14. Apart from the tumor site(s) amenable for biopsy and IT administration, the patient
             must have ≥ 1 measurable lesion, that will be assessed for tumor response following
             RECIST and iRECIST during study conduct.

             Treatment Group 2, Group 4, Group C, or Group F, without intratumoral administration

         15. Documentation of confirmed HPV 16+ non-HNSCC cancer via genotype testing as specified.

         16. Patients who have had tumor progression or recurrence on standard of care therapy,
             including ≥ 1 systemic therapy, or for patients for whom standard of care therapy is
             contraindicated.

         17. Tumor tissue (archival [no older than two years] or able to provide fresh biopsy
             specimen during Screening) collected following the patient's progression from the last
             treatment,unless agreed otherwise between the Sponsor and the Investigator.

             Treatment Group B or Group E

         18. Documentation of confirmed HPV 16+ HNSCC via genotype testing as specified.

         19. Patient must be eligible, as per standard of care, to receive nivolumab (i.e., naïve
             to PD L1 therapy and have progressed on platinum-based therapy).

         20. Tumor tissue (archival [no older than 2 years] or able to provide fresh biopsy
             specimen during Screening) collected following the patient's progression from the last
             treatment,unless agreed otherwise between the Sponsor and the Investigator.

             Contraceptive Criteria (all groups):

         21. Female patients who are of childbearing potential must have a negative serum β human
             chorionic gonadotrophin (β-hCG) pregnancy test prior to the first administration of
             study treatment or be surgically/biologically sterile (hysterectomy or bilateral
             oophorectomy) or postmenopausal.

         22. Patients must agree to 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.

         23. Female patients of childbearing potential can participate in the study if they agree
             to use highly effective contraception from signing of the ICF through five months
             after the last study treatment administration.

         24. Male patients with sexual partners of childbearing potential can participate in the
             study if they agree to use barrier contraception from signing of the ICF through five
             months after the last study treatment administration.

        Exclusion Criteria

        All Patients:

          1. Patients with untreated and/or symptomatic metastatic central nervous system (CNS)
             disease. However, patients with brain/CNS metastases who have undergone surgery or
             radiotherapy, whose disease is stable and who have been on a stable dose of
             corticosteroids (≤ 10 mg prednisone or equivalent) for ≥ 4 weeks prior to the first
             administration of study treatment will be eligible.

          2. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator,
             may increase the risk associated with study participation or study treatment
             administration, impair the ability of the patient to receive study treatment, or
             interfere with the interpretation of the study results. This includes clinically
             significant (i.e., active) cardiovascular disease, including cerebral vascular
             accident/stroke and myocardial infarction less than six months prior to enrollment,
             unstable angina, congestive heart failure (New York Heart Association Classification
             Class II), or serious uncontrolled cardiac arrhythmias.

          3. Concurrent malignancy that is clinically significant or requires active intervention
             at the time of Screening (with the exception of adequately treated, basal or squamous
             cell carcinoma, non melanomatous skin cancer), unless agreed otherwise between the
             Sponsor and the Investigator.

          4. 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.

          5. All toxicities attributed to systemic prior anticancer therapy other than alopecia and
             fatigue that have not resolved to Grade 1 or baseline prior to the first
             administration of study treatment. Patients with toxicities attributed to systemic
             prior anticancer therapy, which are not expected to resolve and result in long lasting
             sequelae, such as neuropathy or ototoxicity after platinum-based therapy, are
             permitted to enroll.

          6. Treatment with any chemotherapy, biological, or investigational therapy for cancer
             within 28 days of the first administration of study treatment.

          7. Treatment with immunosuppressive doses of systemic medication, such as steroids or
             absorbed topical steroids (doses > 10 mg/day prednisone or equivalent), within 14 days
             of the first administration of study treatment.

          8. Treatment with any chronic immunosuppressive medication within six months prior to the
             first administration of study treatment.

          9. Patients who have had a prior anaphylactic or other severe reaction to human
             immunoglobulin or antibody formulation administration.

         10. Live vaccines within 28 days prior to the first dose of study treatment.

         11. 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.

         12. Female patients who are pregnant, breastfeeding, or plan on becoming pregnant during
             the study.

         13. Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
             antibody, indicating acute or chronic infection. Patients who test positive for HCV
             antibody but negative for HCV ribonucleic acid (RNA) are permitted to enroll.

         14. Known history of acquired immunodeficiency syndrome. Testing for the human
             immunodeficiency virus is not mandatory.

         15. Other concurrent severe and/or uncontrolled medical conditions that would, in the
             Investigator's judgment, contraindicate participation in this study.

         16. Psychological, familial, sociological, or geographical conditions that do not permit
             medical follow-up and compliance with the study protocol.

             Dose Expansion Only: Patients Who Qualify to Receive Nivolumab as Part of Standard of
             Care Treatment

         17. History of severe hypersensitivity reaction to nivolumab.

         18. Significant advanced pulmonary disease at Screening

         19. History of untreated tuberculosis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I Dose Escalation: Determine Phase II dose based on incidence of dose-limiting toxicities.
Time Frame:From dosing until 21-28 days after first dose
Safety Issue:
Description:Determine the recommended Phase II dose in terms of safety and tolerability for HB-201 IV and IT and HB-202 IV by assessing drug limiting toxicities.

Secondary Outcome Measures

Measure:Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity).
Time Frame:From informed consent through 30 days after last dose.
Safety Issue:
Description:Assess the safety and tolerability of dosage regimens of HB-201 and HB-202 by monitoring the type, frequency, and severity of AEs and SAEs by monitoring the type, frequency, and severity of AEs and SAEs.
Measure:Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate.
Time Frame:Up to 30-months (until progression)
Safety Issue:
Description:Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using RECIST and iRECIST to determine objective response rate and disease control rate.
Measure:Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity.
Time Frame:Up to 30-months (until progression)
Safety Issue:
Description:Confirm duration of preliminary antitumor activity of dosage regimens of HB-201 and HB-202, using RECIST and iRECIST to determine overall survival, progression-free survival, and duration of response.
Measure:Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity).
Time Frame:Up to 30-months (until progression)
Safety Issue:
Description:Assess the safety and tolerability of dosage regimens of HB-201 and HB-202 by monitoring the type, frequency, and severity of AEs and SAEs.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hookipa Biotech

Trial Keywords

  • Vaccine
  • Gene Therapy
  • TheraT®
  • E7E6
  • HPV 16 E7E6
  • HNSCC
  • HPV 16+ head and neck squamous cell cancer
  • Oropharyngeal cancer
  • Penile cancer
  • Anal cancer
  • Cervical cancer
  • Vaginal cancer
  • Vulvar cancer

Last Updated

June 22, 2020