A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC

Squamous Cell Carcinoma of the Oropharynx Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04398524
• Other study ID #: ISA101b-OPC-03-19
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 1, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2024
• Source: ISA Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Oropharynx

Intervention

Drug:
• ISA101b
ISA101b 4 times plus cemiplimab every 3 weeks for up to 24 months

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
ISA Pharmaceuticals	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  France,  Germany,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate based on radiographic response	Measured by RECIST version 1.1.	20-25 monhts