Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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. - 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, per standard of care, to receive immune checkpoint inhibitor. 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: HB-201 intravenous administration at recommended phase II dose and determined schedule.
    Dose Expansion
Experimental
Ph II, Group B
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive immune checkpoint inhibitor as part of standard of care.
  • Drug: HB-201 intravenous administration at recommended phase II dose and determined schedule + immune checkpoint inhibitor per standard of care.
    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: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule.
    Dose Expansion
Experimental
Ph II, Group E
Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care and are eligible to receive immune checkpoint inhibitor as part of standard of care.
  • Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration at recommended phase II doses and determined schedule + immune checkpoint inhibitor.
    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

Recruiting Locations

O'Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama 35294
Contact:
Ashley M Anderson
205-966-0882
ashau82@uab.edu

More Details

Status
Recruiting
Sponsor
Hookipa Biotech GmbH

Study Contact

General Hookipa contact
+43 1 890 6360
office@hookipabiotech.com

Detailed Description

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 three treatment groups evaluating HB-201 single vector therapy (Groups 1, 2 and 5) and three treatment groups evaluating HB-201 & HB-202 two-vector therapy (Groups 3, 4 and 6). Group 1 and Group 2 Phase I Dose Escalation will determine a safe recommended Phase II dose of HB-201. Group 3 and Group 4 Phase I Dose Escalation will determine a safe RP2D of HB-202. 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. Initial cohorts of HB-201 and/or HB-202 in combination with a checkpoint inhibitor may also be evaluated 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.