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

• ClinicalTrials.gov Identifier: NCT04180215
• Recruitment Status: Recruiting
• First Posted: November 27, 2019
• Last Update Posted: May 15, 2024
• Sponsor: Hookipa Biotech GmbH
• Information provided by (Responsible Party): Hookipa Biotech GmbH

Tracking Information

• First Submitted Date: September 20, 2019
• First Posted Date: November 27, 2019
• Last Update Posted Date: May 15, 2024
• Actual Study Start Date: December 11, 2019
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2023)

• 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, and intravenously administered HB-202 by assessing drug limiting toxicities.
• Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response 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) to determine objective response rate (ORR).

Original Primary Outcome Measures (submitted: November 25, 2019)

• Recommended Phase 2 Dose (RP2D) for IV administration [ Time Frame: 1 year ]
  To determine the RP2D for IV administration of HB-201 in terms of safety and tolerability in patients with HPV 16+ confirmed advanced, recurrent, or metastatic HNSCC
• Recommended Phase 2 Dose (RP2D) for IT administration [ Time Frame: 1 year ]
  To determine the RP2D for IT administration of HB-201 in terms of safety and tolerability in patients with HPV 16+ confirmed cancers

Current Secondary Outcome Measures (submitted: June 23, 2023)

• 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.
• 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
• 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 alone of in combination with pembrolizumab, using RECIST and iRECIST
• 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 alone or in combination with pembrolizumab by monitoring the type, frequency, and severity of AEs and SAEs.

Original Secondary Outcome Measures (submitted: November 25, 2019)

• Number of patients receiving IV HB-201 experiencing treatment-emergent adverse events. [ Time Frame: 1 year ]
  Adverse events that first occurred or worsened in severity after the first administration of study drug and prior to 30 days after the last administration of study treatment will be included.
• Number of patients receiving IT HB-201 experiencing treatment-emergent adverse events [ Time Frame: 1 year ]
  Adverse Events that first occurred or worsened in severity after the first administration of study drug and prior to 30 days after the last administration of study treatment will be included.
• Number of patients receiving IV HB-201 with tumor response throughout the study using RECIST v1.1 and/or iRECIST [ Time Frame: 1 year ]
  To assess the preliminary antitumor activity of IV administration of HB-201
• Number of patients receiving IT HB-201 with tumor response throughout the study using RECIST v1.1 and/or iRECIST [ Time Frame: 1 year ]
  To assess the preliminary antitumor activity of IT administration of HB-201
• Characterization of preliminary immunogenic properties of IV administration by intracellular staining and ELISpot assay. [ Time Frame: 1 year ]
  To characterize the preliminary immunogenic properties of IT administration of HB-201 followed by IV administration of HB-201 in patients with HPV 16+ confirmed cancers.
• Characterization of preliminary immunogenic properties of IT administration [ Time Frame: 1 year ]
  To characterize the preliminary immunogenic properties of IT administration of HB-201 followed by IV administration of HB-201 in patients with HPV 16+ confirmed cancers.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other 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
• Brief Summary: This is a 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.

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.

The trial is enrolling 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. This trial is also enrolling patients with metastatic/recurrent head and neck who have received prior treatment in this setting (2L+, second and later line) who are eligible to receive pembrolizumab as part of their standard of care. Patients will receive the study drugs in addition to their pembrolizumab standard of care regimen.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HPV-Related Squamous Cell Carcinoma

Intervention

• Drug: HB-201 intravenous administration.
  Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort).
• 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).
• Drug: HB-201 intravenous administration + standard of care regimen including pembrolizumab.
  Dose Expansion
• Drug: HB-202 / HB-201 alternating intravenous administration + pembrolizumab.
  Dose Expansion
• Drug: HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab.
  Dose Expansion
• Drug: HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C)
  Dose escalation; 10 patients

Study Arms

• Experimental: Ph I, Group 1 and Group 2
  Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy.
  Intervention: Drug: HB-201 intravenous administration.
• Experimental: Ph I, Group 3 and Group 4
  Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy.
  Intervention: Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration.
• Experimental: Ph II, Group B
  Patients with HPV 16+ HNSCC who are eligible to receive immune checkpoint inhibitor as part of standard of care.
  Intervention: Drug: HB-201 intravenous administration + standard of care regimen including pembrolizumab.
• Experimental: Ph II, Group E
  Patients with HPV 16+ HNSCC who are eligible to receive pembrolizumab as part of 1L standard of care.
  Intervention: Drug: HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab.
• Experimental: Ph II, Group F
  Patients with HPV 16+ cancers who had tumor progression or recurrence on standard of care therapy and who are eligible to receive pembrolizumab as part of 2L+ standard of care..
  Intervention: Drug: HB-202 / HB-201 alternating intravenous administration + pembrolizumab.
• Experimental: Ph I, sub-study
  Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy
  Intervention: Drug: HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 18, 2021): 200
• Original Estimated Enrollment (submitted: November 25, 2019): 100
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility 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 E or Group F:

• Documentation of confirmed head and neck squamous cell carcinoma.
• Eligible to receive pembrolizumab, per standard of care and product label.
• Group E: this group includes first line / 1L patients who have not yet received treatment in the metastatic/recurrent setting.
• Group F: 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:

• Metastatic central nervous system disease, and/or carcinomatous meningitis.
• 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 are met.
• Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy.
• Has a life expectancy of less than 3 months.
• 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 reaction to or known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
• 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 E or F and certain backfill cohorts:

• History of severe hypersensitivity reaction to or other contraindication to receiving pembrolizumab.
• History of/Presently having non-infectious pneumonitis requiring treatment.
• Was discontinued due to a Grade 3 or higher immune-related AE (irAE) after receiving prior therapy with check point inhibitors.

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 3

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: General Hookipa Contact; 1-866-544-8544; hookipa@careboxhealth.com

Contact: Backup Hookipa Contact; clinicaltrials@hookipapharma.com

• Listed Location Countries: Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT04180215
• Other Study ID Numbers: H-200-001; 2019-000907-34 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hookipa Biotech GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Hookipa Biotech GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chief Medical Officer; Hookipa Biotech GmbH

• PRS Account: Hookipa Biotech GmbH
• Verification Date: May 2024