Clinical trial NCT04398524: A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC
Official title: A Phase II Study of Cemiplimab, an Anti-PD-1 Monoclonal Antibody, and ISA101b Vaccine in Patients With Recurrent/Metastatic HPV16 Positive Oropharyngeal Cancer Who Have Experienced Disease Progression With Prior Anti-PD-1 Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Oropharynx
Lead sponsor: ISA Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-05-21
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This will be an open-label, phase 2 study in which subjects will receive ISA101b and cemiplimab.

Detailed description: This study will assess the ability of ISA101b plus cemiplimab to improve Overall Response Rate in subjects who have progressed on prior anti-PD-1 therapy.

Eligibility criteria: Inclusion Criteria:

* Men and women ≥ 18 years of age.
* Provide informed consent signed by study patient.
* Willing and able to comply with site visits and study-related procedures and requirements.
* Histologically confirmed recurrent or metastatic HPV16 positive OPC. Patients with squamous cell carcinoma of occult primary site, presenting with lymph node(s) limited only to the neck, are also eligible. Patients should have HPV16 positivity confirmed before being considered a candidate for this study.
* HPV16 genotyping as determined by a specified central reference laboratory. If local specific HPV16 genotype assessment has been performed, the patient can be enrolled if the result shows HPV16 positivity. Confirmation of HPV16 positive status will then subsequently have to be performed by the central laboratory.
* Patients who have received a minimum total dose of 600 mg of pembrolizumab or 960 mg of nivolumab or equivalent anti-PD-1 antibody with or without chemotherapy for only 1st or 2nd line recurrent/ metastatic HPV16 positive OPC. The last dose of anti-PD-1 must have been no more than 6 months prior to the first dose of study drug. Progressive disease (PD) must have been diagnosed during or after anti-PD-1 therapy (but not longer than 6 months after the last dose), and anti PD-1 therapy (as 1st or 2nd line for recurrent/metastatic HPV16 positive OPC) should have been the last treatment regimen that the patient received before entry into the current trial.
* At least one measurable lesion by CT or MRI per RECIST version 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented disease progression in that site.
* Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria:

* Invasive surgery (defined as surgical intervention requiring general or spinal anesthesia and hospital admission) within 4 weeks prior to start of study treatment.
* Patients who, after progressing on anti-PD-1, received additional anti-cancer therapy (chemotherapy, radiotherapy, experimental TKI's, immunotherapy, anti-EGFR antibodies, surgery). The following palliative treatments are allowed:
* palliative radiotherapy (but NOT for target lesions)
* palliative surgery
* bone resorptive therapy such as bisphosphonates and denosumab but only if patients have been on stable doses for \> 4 weeks prior to first dose of test treatment
* Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug-related toxicity.
* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment.
* Untreated or active primary brain tumor, central nervous system (CNS) metastases, leptomeningeal disease or spinal cord compression.
* Encephalitis, meningitis, organic brain disease (e.g. Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study therapy.
* Known history of, or any evidence of interstitial lung disease, or active, non-infectious pneumonitis (in the past 5 years). A history of radiation pneumonitis in the radiation field is permitted.

Primary outcomes:
measure: Objective Response Rate based on radiographic response
timeFrame: 20-25 monhts
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Olomouc
country: Czechia
facility: Clinic of Oncology
city: Prague
country: Czechia
facility: Institute of Radiation Oncology
city: Prague
country: Czechia
facility: University Hospital Motol, Clinic of Oncology
city: Bordeaux
country: France
facility: Saint Andre Hospital, Department of Oncology
city: Lyon
country: France
facility: Leon Berard Center, Department of Medical Oncology
city: Marseille
country: France
facility: CHU La Timone - La Timone Children's Hospital
city: Paris
country: France
facility: Georges Pompidou European Hospital
city: Reims
country: France
facility: Jean Godinot Institute, Cancer Research Center
city: Strasbourg
country: France
facility: Paul Strauss Center
city: Villejuif
country: France
facility: Gustave Roussy Institute
city: Cologne
country: Germany
facility: University Hospital Cologne, Department of Otorhinolaryngology (ENT)
city: Gießen
country: Germany
facility: University Hospital Giessen and Marburg GmbH
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Saarbruecken
country: Germany
facility: Caritas Klinikum
city: Ulm
country: Germany
facility: University Hospital Ulm
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Cente
city: Brescia
country: Italy
facility: Università degli Studi di Brescia
city: Milan
country: Italy
facility: European Institute of Oncology (IEO), IRCCS, Department of Otolaryngology and Facial Cervix Surgery
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: National Cancer Institute - IRCCS
city: Turin
country: Italy
facility: Institute of Cancer Research and Treatment of Candiolo
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Hospitalet de Llobregat
country: Spain
facility: Catalan Institute of Oncology, Hospital Duran i Reynals, Department of Oncology
city: Madrid
country: Spain
facility: University Clinic of Navarra - Madrid
city: Pamplona
country: Spain
facility: University Clinic of Navarra
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Sutton
Study officials:
References: