E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Human papilloma virus (HPV 16) associated cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10081287 |
E.1.2 | Term | HPV positive oropharyngeal squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063569 |
E.1.2 | Term | Metastatic squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046885 |
E.1.2 | Term | Vaginal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061424 |
E.1.2 | Term | Anal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034299 |
E.1.2 | Term | Penile cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047777 |
E.1.2 | Term | Vulvar cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I Dose Escalation 1.To determine the RP2D in terms of safety and tolerability for: •IV admin of HB-201 in patients with HPV 16+ confirmed HNSCC •IT admin of HB-201 in patients with HPV 16+ confirmed cancers •IV admin of HB-202 in patients with HPV 16+ confirmed HNSCC •IV admin of HB-202 in patients with HPV 16+ confirmed cancers Phase II Dose Expansion 1. To assess the preliminary antitumor activity of: •IV admin of HB-201 in patients with HPV 16+ confirmed HNSCC •IT admin of HB-201 followed by IV administration of HB-201 in patients with HPV 16+ confirmed cancers •IV administration of HB 201 in combination with pembrolizumab in patients with HPV 16+ confirmed HNSCC •Sequential alternating IV admin of HB-201 & HB-202 in patients with HPV 16+ confirmed HNSCC •IT admin of HB-201 followed by sequential alternating IV admin of HB 201 & HB 202 in patients with HPV 16+ confirmed cancers Please refer to Protocol section for full list in Protocol section 2. |
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E.2.2 | Secondary objectives of the trial |
Phase I Dose Escalation 1. To assess the safety and tolerability of: •IV admin of HB-201 in patients with HPV 16+ confirmed HNSCC •IT admin of HB-201 followed by IV administration of HB 201 in patients with HPV 16+ confirmed cancers •Sequential alternating IV administration of HB 201 & HB 202 in patients with HPV 16+ confirmed HNSCC •IT admin of HB-201 followed by sequential alternating IV administration of HB 201 & HB 202 in patients with HPV 16+ confirmed cancers •HB-201 in combination with pembrolizumab in patients with HPV 16+ confirmed cancers •HB-201 & HB-202 alternating two-vector therapy in combination with pembrolizumab in patients with HPV 16+ confirmed cancers. 2. To assess the preliminary antitumor activity of: •IV admin of HB-201 as a continuous in patients with HPV 16+ confirmed HNSCC •IV administration of HB 201 as a 3-dose treatment in patients with HPV 16+ confirmed HNSCC Phase II Dose Expansion Please refer to Protocol section for full list in Protocol section 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Patients: -18 years of age or older -≥ 1 measurable lesion by imaging for tumor response following RECIST and iRECIST -ECOG performance status of 0 to 1. -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. -Screening laboratory values must meet protocol-specified criteria Treatment Group 1, Group 3, Group 4, Group 5 Group A, or Group D: -Documentation of confirmed HPV 16+ HNSCC via genotype testing -Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy or be a patient for whom standard of care therapy is contraindicated. Treatment Group 2, Group 4, Group C, or Group F: -Documentation of confirmed HPV 16+ cancer via genotype testing -Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy -Safe and accessible tumor site amenable for biopsy and IT administration -Apart from the tumor site(s) amenable for biopsy and IT administration ≥ 1 measurable lesion for RECIST assessment - Female patients who are of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test prior to the first administration of study treatment or be surgically/biologically sterile (hysterectomy or bilateral oophorectomy) or postmenopausal. - 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 5 months after the last study treatment administration. Treatment Group B or Group E: -Documentation of confirmed HPV 16+ HNSCC via genotype testing -Must be eligible, as per standard of care, to receive pembrolizumab |
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E.4 | Principal exclusion criteria |
-Untreated and/or symptomatic metastatic central nervous system (CNS) disease, and/or carcinomatous meningitis. With some exceptions for treated and stable brain/CNS metastases -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 -Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy -Toxicity attributed to systemic prior anticancer therapy, including radiation and surgery, other than alopecia and fatigue that has not resolved to Grade 1 or Baseline prior to the first administration of study -Not meeting the protocol-specified washout periods for prohibited medications per the protocol -Treatment with any chemotherapy, biological, or investigational therapy for cancer within 28 days of the first administration of study treatment., unless agreed otherwise between the Sponsor and the Investigator on a case-by-case basis based on the half-life of the anticancer therapy. Exception: Ongoing treatment with pembrolizumab is permitted if the subject is enrolling in a backfill cohort continuing pembrolizumab and adding either HB-201 monotherapy or HB-201 & HB-202 alternating two vector therapy. -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 AIDS. For patients receiving pembrolizumab: -History of severe hypersensitivity reaction to pembrolizumab -Any contraindication to receiving pembrolizumab per package insert or SmPC -Allogeneic tissue/solid organ transplant. -History of (non-infectious) pneumonitis that required steroids or current pneumonitis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I Dose Escalation •Incidence of DLTs from the first study drug administered during the DLT observation period
Phase II Dose Expansion Tumor responses will be assessed using RECIST and iRECIST by the Investigator: •Objective response rate •Disease control rate
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Phase I Dose Escalation •Safety: type, frequency, and severity of AEs and SAEs •Tolerability: dose interruptions, reductions and dose intensity, and evaluations of laboratory values •Tumor responses will be assessed using RECIST and iRECIST by the Investigator: -Objective response rate -Disease control rate
Phase II Dose Expansion Tumor responses will be assessed using RECIST and iRECIST by the Investigator: •Overall survival •Progression-free survival •Duration of response
•Safety: type, frequency, and severity of AEs and SAEs •Tolerability: dose interruptions, reductions and dose intensity, and evaluations of laboratory values
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 12 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
European Union |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end when long-term follow up (including progression-free survival and/or overall survival) has been completed for all patients as described in Section 6.1.5, or in the event of early termination of the study (Section 3.3).
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |