A Study of TheraT® Vector(s) Expressing HPV 16+ in Patients With HPV 16+ Confirmed Cancers
- Interventional
- Recruiting
- NCT04180215
Contact Information
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
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.
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 two treatment groups evaluating HB-201 single vector therapy (Groups 1 and 2) and two treatment groups evaluating HB-201 & HB-202 two-vector therapy (Groups 3 and 4). Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose of HB-201 for intravenous (IV) and intratumoral treatment. Group 3 and Group 4 Phase I Dose Escalation will determine a safe RP2D of HB-202 for IV treatment. 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.
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.
Phase I Dose Escalation will comprise two treatment groups evaluating HB-201 single vector therapy (Groups 1 and 2) and two treatment groups evaluating HB-201 & HB-202 two-vector therapy (Groups 3 and 4). Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose of HB-201 for intravenous (IV) and intratumoral treatment. Group 3 and Group 4 Phase I Dose Escalation will determine a safe RP2D of HB-202 for IV treatment. 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.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
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.
Treatment Group 1, Group 3, 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.
- Able to provide tumor tissue following last treatment, unless otherwise agreed.
Treatment Group 2, Group 4, Group C, or Group F:
- Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy.
- Safe and accessible tumor site amenable for biopsy and intratumoral administration.
- Apart from the tumor site(s) amenable for biopsy and IT administration, ≥ 1 measurable lesion for RECIST assessment.
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.
- Able to provide tumor tissue following last treatment, unless otherwise agreed.
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
• History of severe hypersensitivity reaction to or other contraindication to receiving immune checkpoint inhibitor.
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.
Treatment Group 1, Group 3, 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.
- Able to provide tumor tissue following last treatment, unless otherwise agreed.
Treatment Group 2, Group 4, Group C, or Group F:
- Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy.
- Safe and accessible tumor site amenable for biopsy and intratumoral administration.
- Apart from the tumor site(s) amenable for biopsy and IT administration, ≥ 1 measurable lesion for RECIST assessment.
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.
- Able to provide tumor tissue following last treatment, unless otherwise agreed.
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
• History of severe hypersensitivity reaction to or other contraindication to receiving immune checkpoint inhibitor.