A Phase 1/2 Study in Patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers
- Conditions
- HPV-Related Squamous Cell Carcinoma
- Interventions
- Drug: HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab.Drug: HB-202 / HB-201 alternating intravenous administration + pembrolizumab.Drug: HB-201 intravenous administration.Drug: HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C)Drug: HB-201 intravenous administration + standard of care regimen including pembrolizumab.Drug: HB-202 intravenous administration alternating with HB-201 intravenous administration.
- Registration Number
- NCT04180215
- Lead Sponsor
- Hookipa Biotech GmbH
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Ph II, Group E HB-202 / HB-201 alternating intravenous administration + standard of care regimen including pembrolizumab. Patients with HPV 16+ HNSCC who are eligible to receive pembrolizumab as part of 1L standard of care. Ph II, Group F HB-202 / HB-201 alternating intravenous administration + pembrolizumab. Patients with HPV 16+ cancers who had tumor progression or recurrence on standard of care therapy and who are eligible to receive pembrolizumab as part of 2L+ standard of care.. Ph I, Group 1 and Group 2 HB-201 intravenous administration. Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy. Ph I, sub-study HB-201 or HB-201/HB-202 alternating treatment using CD8 PET Tracer (Zr-Df-IAB22M2C) Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy Ph II, Group B HB-201 intravenous administration + standard of care regimen including pembrolizumab. Patients with HPV 16+ HNSCC who are eligible to receive immune checkpoint inhibitor as part of standard of care. Ph I, Group 3 and Group 4 HB-202 intravenous administration alternating with HB-201 intravenous administration. Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy.
- Primary Outcome Measures
Name Time Method Phase I Dose Escalation: Determine Phase II dose based on incidence of dose-limiting toxicities. From dosing until 21-28 days after first dose 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.
Phase II Dose Expansion: Number of participants with preliminary antitumor activity based on objective response rate. Until progression, (estimated up to 30-months) 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).
- Secondary Outcome Measures
Name Time Method Phase I Dose Escalation: Number of participants with preliminary antitumor activity based on objective response rate and disease control rate. Until progression, (estimated up to 30-months) Assess the preliminary antitumor activity of dosage regimens of HB-201 and HB-202 using RECIST and iRECIST
Phase I Dose Escalation: Number of participants with adverse events (type, frequency, severity). From informed consent through 30 days after last dose. 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.
Phase II Dose Expansion: Number of participants with confirmed duration of preliminary antitumor activity. Up to 30-months (until progression) 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
Phase II Dose Expansion: Number of participants with adverse events (type, frequency, severity). From informed consent through 30 days after last dose 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.
Trial Locations
- Locations (34)
O'Neal Comprehensive Cancer Center at UAB
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Arkansas for Medical Sciences, Cancer Institute, Clinical Trials Office
🇺🇸Fayetteville, Arkansas, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA (University of California, Los Angeles)
🇺🇸Los Angeles, California, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Loyola University Medical School
🇺🇸Maywood, Illinois, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸St Louis, Missouri, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Montefiore-Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Grossman School of Medicine
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Perlmutter Cancer Center at NYU Langone Hospital-Long Island
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, 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 Virgina Health System
🇺🇸Charlottesville, Virginia, United States
Froedtert Hospital and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Amsterdam UMC, Locatie VUMC
🇳🇱Amsterdam, Netherlands
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain