Clinical trial NCT04180215: A Phase 1/2 Study in Patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: HPV-Related Squamous Cell Carcinoma
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
Lead sponsor: Hookipa Biotech GmbH
Sponsor class: INDUSTRY
First posted: 2019-11-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Phase I Dose Escalation: Determine Phase II dose based on incidence of dose-limiting toxicities.
timeFrame: From dosing until 21-28 days after first dose
measure: Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response rate.
timeFrame: Until progression, (estimated up to 30-months)
Secondary outcomes:
measure: Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity).
timeFrame: From informed consent through 30 days after last dose.
measure: Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate.
timeFrame: Until progression, (estimated up to 30-months)
measure: Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity.
timeFrame: Up to 30-months (until progression)
measure: Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity).
timeFrame: From informed consent through 30 days after last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center at UAB
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Fayetteville
country: United States
facility: University of Arkansas for Medical Sciences, Cancer Institute, Clinical Trials Office
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA (University of California, Los Angeles)
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical School
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: St Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore-Einstein Center for Cancer Care
state: New York
city: New York
country: United States
facility: Grossman School of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital-Long Island
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center (ITOR)
state: South Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virgina Health System
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital and Medical College of Wisconsin
state: Wisconsin
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie VUMC
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Hookipa Biotech GmbH
name: Head of Clinical Development
role: STUDY_DIRECTOR
References: