A Study of TheraT® Vector(s) Expressing HPV 16+ in Patients With HPV 16+ Confirmed Cancers

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

  • HPV-Related Squamous Cell Carcinoma

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. 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.

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

Recruiting Locations

Montefiore-Einstein Center for Cancer Care
Bronx, New York 10461
Contact:
Mohammad Ghalib
718-405-8515
mhghalib@montefiore.org

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 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.