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A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers

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ClinicalTrials.gov Identifier: NCT04180215
Recruitment Status : Recruiting
First Posted : November 27, 2019
Last Update Posted : November 18, 2022
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: Immune checkpoint inhibitor regimen per standard of care + HB-201 intravenous administration. Drug: HB-201 intravenous administration + standard of care regimen including pembrolizumab. 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: Immune checkpoint inhibitor regimen per standard of care + HB-202/HB-201 alternating 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 at recommended phase II dose. Drug: HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab. 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 study drugs which are designed to train the body to recognize and fight substances found in HPV 16+ cancer. This trial studies the safety and anti-cancer effect of HB-201 and HB-202 in people.

This trial is enrolling patients who have HPV16+ cancers of any type and have received prior therapy in the metastatic/recurrent setting.

The trial also enrolls patients with metastatic/recurrent head and neck cancer who have not yet received treatment in this setting (1L, first line) and who are eligible to receive pembrolizumab as part of their standard of care. Patients in this group will receive the study drugs in addition to their pembrolizumab standard of care regimen.

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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 : June 2023
Estimated Study Completion Date : June 2025


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: Immune checkpoint inhibitor regimen per standard of care + HB-201 intravenous administration.
Dose Expansion

Experimental: Ph II, Group B
Patients with HPV 16+ HNSCC who are eligible to receive immune checkpoint inhibitor as part of standard of care.
Drug: HB-201 intravenous administration + standard of care regimen including pembrolizumab.
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: Immune checkpoint inhibitor regimen per standard of care + HB-202/HB-201 alternating intravenous administration.
Dose Expansion

Experimental: Ph II, Group E
Patients with HPV 16+ HNSCC who are eligible to receive immune checkpoint inhibitor as part of standard of care.
Drug: HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab.
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 to receive pembrolizumab, per standard of care and product label. Note: this group includes first line / 1L patients who have not yet received treatment in the metastatic/recurrent setting.

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 1-866-544-8544 hookipa@careboxhealth.com
Contact: Backup Hookipa Contact clinicaltrials@hookipapharma.com

Locations
Show Show 23 study locations
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 18, 2022
Last Verified: November 2022
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
HPV16
HPV 16
Head and neck cancer
Carcinoma
Carcinoma, squamous cell
Squamous cell carcinoma of head and neck
Neoplasms, squamous cell
Head and neck neoplasms
Pembrolizumab
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pembrolizumab
Immune Checkpoint Inhibitors
Antineoplastic Agents, Immunological
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action