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

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ClinicalTrials.gov Identifier: NCT04180215
Recruitment Status : Recruiting
First Posted : November 27, 2019
Last Update Posted : November 16, 2021
Sponsor:
Information provided by (Responsible Party):
Hookipa Biotech GmbH

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HPV-Related Squamous Cell Carcinoma Drug: HB-201 intravenous administration. Drug: HB-201 intratumoral administration for first dose, followed by HB-201 intravenous administration for subsequent doses. Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration. Drug: HB-201 intratumoral administration for first dose; followed by HB-202 intravenous administration alternating with HB-201 intravenous administration for subsequent doses. Drug: HB-201 intravenous administration at recommended phase II dose and determined schedule. Drug: HB-201 intravenous administration at recommended phase II dose and determined schedule + immune checkpoint inhibitor per standard of care. Drug: HB-201 intratumoral administration for first dose followed by HB-201 intravenous administration for subsequent doses at recommended phase II dose and determined schedule. Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule. Drug: HB-201 intratumoral administration for first dose; followed by HB-202 intravenous administration alternating with HB-201 intravenous administration for subsequent doses at recommended phase II dose. Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule + immune checkpoint inhibitor. Drug: HB-201 intravenous administration for a limited number of dose administration. Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration for a limited number of dose administration Drug: HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C) Phase 1 Phase 2

Detailed Description:

HB-201 and HB-202 are 'vectors', modified viruses intended to train the body to recognize antigens found in HPV 16+ cancer.

Phase I Dose Escalation will comprise three treatment groups evaluating HB-201 single vector therapy (Groups 1, 2 and 5) and three treatment groups evaluating HB-201 & HB-202 two-vector therapy (Groups 3, 4 and 6). Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose of HB-201. Group 3 and Group 4 Phase I Dose Escalation will determine a safe RP2D of HB-202. Various doses of the investigational therapies (HB-201 and HB-202) and dosing schedules may be evaluated in separate groups of patients (cohorts) during Phase I Dose Escalation. Initial cohorts of HB-201 and/or HB-202 in combination with a checkpoint inhibitor may also be evaluated during Phase I Dose Escalation.

Phase II Dose Expansion may have up to six treatment groups (Groups A to F) with HB-201 and HB-202 administered at the recommended Phase II doses and the dosing schedule determined during Phase I Dose Escalation. Potential groups will explore the following treatments: HB-201 single vector therapy; HB-201 & HB-202 two-vector therapy; HB-201 single vector therapy in combination with an immune checkpoint inhibitor; and/or HB-201 & HB-202 two-vector in combination with an immune checkpoint inhibitor.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ph I, Group 1
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
Drug: HB-201 intravenous administration.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort).

Experimental: Ph I, Group 2
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.
Drug: HB-201 intratumoral administration for first dose, followed by HB-201 intravenous administration for subsequent doses.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort)

Experimental: Ph I, Group 3
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort).

Experimental: Ph I, Group 4
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.
Drug: HB-201 intratumoral administration for first dose; followed by HB-202 intravenous administration alternating with HB-201 intravenous administration for subsequent doses.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort)

Experimental: Ph II, Group A
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
Drug: HB-201 intravenous administration at recommended phase II dose and determined schedule.
Dose Expansion

Experimental: Ph II, Group B
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive immune checkpoint inhibitor as part of standard of care.
Drug: HB-201 intravenous administration at recommended phase II dose and determined schedule + immune checkpoint inhibitor per standard of care.
Dose Expansion

Experimental: Ph II, Group C
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.
Drug: HB-201 intratumoral administration for first dose followed by HB-201 intravenous administration for subsequent doses at recommended phase II dose and determined schedule.
Dose Expansion

Experimental: Ph II, Group D
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule.
Dose Expansion

Experimental: Ph II, Group E
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive immune checkpoint inhibitor as part of standard of care.
Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule + immune checkpoint inhibitor.
Dose Expansion

Experimental: Ph II, Group F
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.
Drug: HB-201 intratumoral administration for first dose; followed by HB-202 intravenous administration alternating with HB-201 intravenous administration for subsequent doses at recommended phase II dose.
Dose Expansion

Experimental: Ph I, Group 5
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy.
Drug: HB-201 intravenous administration for a limited number of dose administration.
Dose/Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort)

Experimental: Ph I, Group 6
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy
Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration for a limited number of dose administration
Dose/Schedule determined by 3+3 dose escalation

Experimental: Ph I, sub-study
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy
Drug: HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C)
Dose escalation; 10 patients




Primary Outcome Measures :
  1. 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 ]
    Determine the recommended Phase II dose in terms of safety and tolerability for intravenously administered HB-201, intratumorally administered HB-201, and intravenously administered HB-202 by assessing drug limiting toxicities.

  2. Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate. [ Time Frame: Until progression, (estimated up to 30-months) ]
    Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using Response Evaluation Criteria in Solid Tumors (RECIST) and immune Response Evaluation Criteria in Solid Tumors (iRECIST) to determine objective response rate and disease control rate.


Secondary Outcome Measures :
  1. Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity). [ Time Frame: From informed consent through 30 days after last dose. ]
    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.

  2. Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate. [ Time Frame: Until progression, (estimated up to 30-months) ]
    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.

  3. Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity. [ Time Frame: Up to 30-months (until progression) ]
    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.

  4. Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity). [ Time Frame: From informed consent through 30 days after last dose ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

All Patients:

  • Documentation of confirmed HPV 16+ cancer via genotype testing.
  • ≥ 1 measurable lesion by imaging for tumor response following RECIST
  • ECOG performance status of 0 to 1.
  • Prior curative radiation therapy and prior focal palliative completed per protocol-specified wash-out windows.
  • Screening laboratory values must meet protocol-specified criteria.
  • Able to provide tumor tissue following last treatment, unless otherwise agreed.

Treatment Group 1, Group 3, Group 5, Group 6, Group A, or Group D:

  • Documentation of confirmed head and neck squamous cell carcinoma.
  • Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy.

Treatment Group 2, Group 4, Group C, or Group F:

• Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy.

Treatment Group B or Group E:

  • Documentation of confirmed head and neck squamous cell carcinoma.
  • Eligible, per standard of care, to receive immune checkpoint inhibitor.

Anal Cancer Cohort:

  • Documentation of confirmed HPV 16+ locally advanced or metastatic SCC of anal canal.
  • Tumor progression or recurrence on standard of care therapy, including ≥1 systemic therapy.

Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):

  • Meeting requirements of inclusion criteria for Treatment Group 1 or Group 3.
  • At least 1 non-irradiated measurable lesion documented through imaging.

Exclusion Criteria:

All patients:

  • Untreated and/or symptomatic metastatic central nervous system disease, unless protocol-defined criteria is met.
  • Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation / treatment administration.
  • Concurrent malignancy that is clinically significant or requires active intervention, unless protocol-defined criteria is met.
  • Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy.
  • Any toxicities attributed to systemic prior anticancer therapy o that have not resolved to Grade 1 or baseline prior to the first administration of study drug, unless protocol-defined criteria is met.
  • Not meeting the protocol-specified washout periods for prohibited medications.
  • Prior anaphylactic or other severe reaction to human immunoglobulin or antibody formulation administration.
  • Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, indicating acute or chronic infection.
  • Known history of acquired immunodeficiency syndrome.

For patients in Groups B or E and certain backfill cohorts:

  • History of severe hypersensitivity reaction to or other contraindication to receiving immune checkpoint inhibitor.
  • Allogenic tissue/solid organ transplant.
  • History of/Presently having non-infectious pneumonitis requiring treatment.

Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):

  • Having splenic disorders or prior splenectomy, and can compromise protocol objectives per Investigator and/or Sponsor.
  • Meeting requirements of exclusion criteria for Treatment Group 1 or Group 3

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04180215


Contacts
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Contact: General Hookipa contact +43 1 890 6360 office@hookipabiotech.com
Contact: Hookipa Backup Contact +1 332 207 4590

Locations
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United States, Alabama
O'Neal Comprehensive Cancer Center at UAB Recruiting
Birmingham, Alabama, United States, 35294
Contact: Ashley M Anderson    205-966-0882    ashau82@uab.edu   
Principal Investigator: Lisle Nabel, MD         
United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Eileen Molzen       Eileen.Molzen@bannerhealth.com   
Contact: Tina Schaffner       Tina.Schaffner@bannerhealth.com   
Principal Investigator: Jiaxin Niu, MD         
United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Jorge Nieva, MD    323-865-3111      
United States, Florida
Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Reisy Guesdes    305-243-8807    rxg957@med.miami.edu   
Principal Investigator: Agustin Pimentel, MD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Alexander Pearson, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Fairway, Kansas, United States, 66205
Contact: KUCC Nurse Navigator    913-588-3671    kucc_navigation@kumc.edu   
Principal Investigator: Prakash Neupane, MD         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Karie Gignac    313-916-7453    kgignac1@hfhs.org   
Principal Investigator: Ding Wang, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nate Beck       nbeck@wustl.edu   
Principal Investigator: Douglas Adkins, MD         
United States, New York
Montefiore-Einstein Center for Cancer Care Recruiting
Bronx, New York, United States, 10461
Contact: Mohammad Ghalib    718-405-8515    mhghalib@montefiore.org   
Principal Investigator: Sanjay Goel, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Libby Warner       warnere@mskcc.org   
Contact: Jamie Walters       waltersj@mskcc.org   
Principal Investigator: David Pfister, MD         
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Michael Posner, MD    212-659-5461      
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Debra Richardson, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Melissa Pomeroy       Melissa.Pomeroy@providence.org   
Principal Investigator: Rom Leidner, MD         
United States, South Carolina
Greenville Hospital System University Medical Center (ITOR) Recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa Johnson    864-455-3735      
Contact: Fiona Davidson    864-455-3737      
Principal Investigator: Ki Chung, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Siquing Fu, MD       siqingfu@mdanderson.org   
United States, Wisconsin
Froedtert Hospital and Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Stuart Wong, MD    414-805-8900    CCCTO@mcw.edu   
Sponsors and Collaborators
Hookipa Biotech GmbH
Investigators
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Study Director: Chief Medical Officer Hookipa Biotech GmbH
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Responsible Party: Hookipa Biotech GmbH
ClinicalTrials.gov Identifier: NCT04180215    
Other Study ID Numbers: H-200-001
2019-000907-34 ( EudraCT Number )
First Posted: November 27, 2019    Key Record Dates
Last Update Posted: November 16, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hookipa Biotech GmbH:
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
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents