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.
Brief Title
A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
HPV-Related Squamous Cell Carcinoma
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
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
Inclusion 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.
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.
Gender
All
Gender Based
false
Keywords
Vaccine
Gene Therapy
TheraT®
E7E6
HPV 16 E7E6
HNSCC
HPV 16+ head and neck squamous cell cancer
Oropharyngeal 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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04180215
Org Class
Industry
Org Full Name
Hookipa Biotech GmbH
Org Study Id
H-200-001
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Phase I Dose Escalation: Determine Phase II dose based on incidence of dose-limiting toxicities.
Outcome Time Frame
From dosing until 21-28 days after first dose
Outcome Description
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).
Outcome Measure
Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response rate.
Outcome Time Frame
Until progression, (estimated up to 30-months)
Secondary Ids
Secondary Id
2019-000907-34
Secondary Outcomes
Outcome 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.
Outcome Time Frame
From informed consent through 30 days after last dose.
Outcome Measure
Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity).
Outcome Description
Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using RECIST and iRECIST
Outcome Time Frame
Until progression, (estimated up to 30-months)
Outcome Measure
Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate.
Outcome Description
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
Outcome Time Frame
Up to 30-months (until progression)
Outcome Measure
Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity.
Outcome Description
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.
Outcome Time Frame
From informed consent through 30 days after last dose
Outcome Measure
Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity).
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enrico Castellucci
Investigator Email
ecastell@montefiore.org