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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Squamous Cell Carcinoma of the Oropharynx
• Intervention / Treatment: Drug: ISA101b

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.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • University Hospital Antwerp
  • Ghent, Belgium
    • University Hospital Ghent
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège
• Czechia
  • Olomouc, Czechia
    • Clinic of Oncology
  • Prague, Czechia
    • Institute of Radiation Oncology
  • Prague, Czechia
    • University Hospital Motol, Clinic of Oncology
• France
  • Bordeaux, France, 33000
    • Saint Andre Hospital, Department of Oncology
  • Lyon, France, 69008
    • Leon Berard Center, Department of Medical Oncology
  • Marseille, France
    • CHU La Timone - La Timone Children's Hospital
  • Paris, France
    • Georges Pompidou European Hospital
  • Reims, France
    • Jean Godinot Institute, Cancer Research Center
  • Strasbourg, France
    • Paul Strauss Center
  • Villejuif, France
    • Gustave Roussy Institute
• Germany
  • Cologne, Germany, 50937
    • University Hospital Cologne, Department of Otorhinolaryngology (ENT)
  • Gießen, Germany
    • University Hospital Giessen and Marburg GmbH
  • Mannheim, Germany
    • University Hospital Mannheim
  • Saarbruecken, Germany
    • Caritas Klinikum
  • Ulm, Germany
    • University Hospital Ulm
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Tel Aviv, Israel
    • The Tel Aviv Sourasky Medical Cente
• Italy
  • Brescia, Italy
    • Università degli Studi di Brescia
  • Milan, Italy
    • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Milan, Italy
    • European Institute of Oncology (IEO), IRCCS, Department of Otolaryngology and Facial Cervix Surgery
  • Naples, Italy
    • National Cancer Institute - IRCCS
  • Turin, Italy, 10060
    • Institute of Cancer Research and Treatment of Candiolo
• Spain
  • Barcelona, Spain
    • University Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clinic of Barcelona
  • Hospitalet de Llobregat, Spain, 08908
    • Catalan Institute of Oncology, Hospital Duran i Reynals, Department of Oncology
  • Madrid, Spain, 28027
    • University Clinic of Navarra - Madrid
  • Pamplona, Spain, 31008
    • University Clinic of Navarra
• United Kingdom
  • London, United Kingdom
    • Royal Marsden Hospital
  • London, United Kingdom
    • Guy's Hospital
  • Sutton, United Kingdom
    • Royal Marsden Hospital - Sutton
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Anschutz Cancer Pavilion
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; ISA101b 4 times plus cemiplimab every 3 weeks for up to 24 months	Drug: ISA101b; ISA101b 4 times plus cemiplimab every 3 weeks for up to 24 months; Other Names: Cemiplimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate based on radiographic response	Measured by RECIST version 1.1.	20-25 monhts

Collaborators and Investigators

• Sponsor: ISA Pharmaceuticals
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 16, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: ISA101b-OPC-03-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No