A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers

HPV-Related Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04180215
• Other study ID #: H-200-001
• Secondary ID: 2019-000907-34
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 11, 2019
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: Hookipa Biotech GmbH
• Contact: General Hookipa Contact
• Phone: 1-866-544-8544
• Email: hookipa[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• HPV-Related Squamous Cell Carcinoma

Intervention

Drug:
• HB-201 intravenous administration.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort).
• HB-202 intravenous administration alternating with HB-201 intravenous administration.
Dose / Schedule determined by 3+3 dose escalation (3 to 6 patients per cohort).
• HB-201 intravenous administration + standard of care regimen including pembrolizumab.
Dose Expansion
• HB-202 / HB-201 alternating intravenous administration + pembrolizumab.
Dose Expansion
• HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab.
Dose Expansion
• HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C)
Dose escalation; 10 patients

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC, Locatie VUMC	Amsterdam
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
United States	O'Neal Comprehensive Cancer Center at UAB	Birmingham	Alabama
United States	Montefiore-Einstein Center for Cancer Care	Bronx	New York
United States	University of Virgina Health System	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Kansas Medical Center	Fairway	Kansas
United States	University of Arkansas for Medical Sciences, Cancer Institute, Clinical Trials Office	Fayetteville	Arkansas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Greenville Hospital System University Medical Center (ITOR)	Greenville	South Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	UCLA (University of California, Los Angeles)	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Loyola University Medical School	Maywood	Illinois
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Grossman School of Medicine	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Perlmutter Cancer Center at NYU Langone Hospital-Long Island	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Hookipa Biotech GmbH

Countries where clinical trial is conducted

United States,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I Dose Escalation: Determine Phase II dose based on incidence of dose-limiting toxicities.	Determine the recommended Phase II dose in terms of safety and tolerability for intravenously administered HB-201, and intravenously administered HB-202 by assessing drug limiting toxicities.	From dosing until 21-28 days after first dose
Primary	Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response rate.	Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using Response Evaluation Criteria in Solid Tumors (RECIST) to determine objective response rate (ORR).	Until progression, (estimated up to 30-months)
Secondary	Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity).	Assess the safety and tolerability of dosage regimens of HB-201 and HB-202 by monitoring the type, frequency, and severity of AEs and SAEs by monitoring the type, frequency, and severity of AEs and SAEs.	From informed consent through 30 days after last dose.
Secondary	Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate.	Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using RECIST and iRECIST	Until progression, (estimated up to 30-months)
Secondary	Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity.	Confirm duration of preliminary antitumor activity of dosage regimens of HB-201 and HB-202 alone of in combination with pembrolizumab, using RECIST and iRECIST	Up to 30-months (until progression)
Secondary	Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity).	Assess the safety and tolerability of dosage regimens of HB-201 and HB-202 alone or in combination with pembrolizumab by monitoring the type, frequency, and severity of AEs and SAEs.	From informed consent through 30 days after last dose