A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC

NCT ID: NCT03669718

Last Updated: 2023-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-30

Study Completion Date

2025-06-30

Brief Summary

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This will be a blinded, placebo-controlled, randomized, phase 2 study in which subjects will be randomly assigned 1:1 to cemiplimab plus placebo or cemiplimab plus ISA101b.

Detailed Description

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This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with HPV16 positive OPC, when combined with cemiplimab, an investigational anti-PD-1 antibody being developed by Regeneron Pharmaceuticals. ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16. Trials in HPV16 driven malignancies indicate it has activity in HPV16 driven malignancies including oropharyngeal and cervical cancers. Cemiplimab, also known as REGN2810, is in late stage trials and appears to have similar activity to approved anti PD-1 antibodies in a number of malignancies .

Conditions

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Squamous Cell Carcinoma of the Oropharynx HPV16 Positive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Active ISA101b and cemiplimab.

ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months

Group Type EXPERIMENTAL

ISA101b

Intervention Type BIOLOGICAL

Every 3 weeks for a total of 3 times

Cemiplimab

Intervention Type DRUG

Every 3 weeks for up to 24 months

Placebo and cemiplimab

Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months

Group Type PLACEBO_COMPARATOR

Cemiplimab

Intervention Type DRUG

Every 3 weeks for up to 24 months

Placebo

Intervention Type OTHER

Every 3 weeks for a total of 3 times

Interventions

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ISA101b

Every 3 weeks for a total of 3 times

Intervention Type BIOLOGICAL

Cemiplimab

Every 3 weeks for up to 24 months

Intervention Type DRUG

Placebo

Every 3 weeks for a total of 3 times

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Males and females, ≥ 18 years of age.
* Sign and date an Institutional Review Board/Independent Ethics Committee (IRB)/(IEC)-approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
* Be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
* Diagnosed with histologically confirmed recurrent or metastatic HPV16 positive OPC, whose tumors express PD-L1 (Combined Positive Score \[CPS\] ≥1) and who are candidates for first line therapy with an PD-1 blocking antibody, AND subjects with recurrent or metastatic HPV16 positive OPC with disease progression on or after platinum containing chemotherapy.
* HPV-16 genotyping will be determined by the specified central reference laboratory.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria.
* Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of study drug.

Exclusion Criteria

* Subjects with previously untreated metastatic or unresectable, recurrent HPV16 positive OPC whose tumors do not express PD-L1 (CPS\<1) and who are therefore not candidates for monotherapy with an anti-PD-1 antibody.
* Subjects with known brain metastases or leptomeningeal metastases.
* Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
* History of other malignancy ≤ 3 years prior to entry into this trial with the exception of basal cell or squamous cell skin carcinoma which were treated with local resection only, or carcinoma in situ of the cervix, prostate or breast, or low grade non-muscle invasive superficial bladder cancer (TaLG)/carcinoma in situ of the bladder.
* Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Subjects with a condition requiring immunosuppressive doses of systemic medication such as steroids or absorbed topical steroids (doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab, cemiplimab), as well as an antibody targeting anti-PL-L1 anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co stimulation or immune checkpoint pathways.
* Prior treatment with more than one chemotherapy regimen for the management of metastatic OPC.
* Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b. Subjects may have received a preventive HPV vaccine.
* All toxicities attributed to systemic prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE) or baseline before administration of study drug. Subjects with toxicities attributed to systemic prior anticancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
* History of allergy to ISA101/ISA101b study drug components, e.g., ISA101/101b, Montanide, or Macrogolglycerol Ricinoleate, also known as cremophore.
* History of allergy to cemiplimab and its excipients.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

ISA Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bonnie S. Glisson, MD, BS

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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City of Hope

Duarte, California, United States

Site Status

Moores Cancer Center at the UC San Diego Health

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

ICAHN School of Medicine at Mount Sinai

New York, New York, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

M. D. Anderson Cancer Center

Houston, Texas, United States

Site Status

University Hospital Antwerp

Antwerp, , Belgium

Site Status

DFSATR/Oncologia D'Or

Brasília, , Brazil

Site Status

Instituto do Cancer do Estado de Sao Paulo

São Paulo, , Brazil

Site Status

University Hospital Olomouc

Olomouc, , Czechia

Site Status

Nemocnice na Bulovce

Prague, , Czechia

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

CHU La Timone

Marseille, , France

Site Status

Antoine Lacassagne Center

Nice, , France

Site Status

Gustave Roussy

Paris, , France

Site Status

Hopitaux Universitaires Pitié Salpêtrière Charles Foix

Paris, , France

Site Status

Universitaetsklinikum Ulm

Ulm, , Germany

Site Status

Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

Site Status

University of Pecs Department of Oncotherapy

Pécs, , Hungary

Site Status

Hetenyi Geza Korhaz-Rendelointezet

Szolnok, , Hungary

Site Status

ASST Spedali Civili Brescia, Department of Medical Oncology

Brescia, , Italy

Site Status

Azienda Ospedaliera San Paolo Polo Universitario

Milan, , Italy

Site Status

Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

National Cancer Institute - IRCCS "Fondazione G. Pascale"

Naples, , Italy

Site Status

National Cancer Institute Regina Elena, IRCCS

Rome, , Italy

Site Status

Consultorio de Oncología Médica

Oaxaca City, , Mexico

Site Status

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status

Maria Sklodowska-Curie National Institute of Oncology

Gliwice, , Poland

Site Status

Swietokrzyskie Oncology Center Kielce

Kielce, , Poland

Site Status

Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status

Hospital Duran i Reynals - Institut Catala dOncologia ICO

Barcelona, , Spain

Site Status

Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Marqués de Valdecilla Santander

Santander, , Spain

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

The Royal Marsden NHS Foundation

Chelsea, , United Kingdom

Site Status

Guy's Hospital

London, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Beacon Centre Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Countries

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United States Belgium Brazil Czechia France Germany Hungary Italy Mexico Netherlands Poland Spain United Kingdom

References

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Even C, Harrington KJ, Massarelli E, Laban S, Fayette J, Oliva M, Klein Hesselink M, Visscher S, Fury MG, Wiekmeijer AS, Licitra L, Melichar B, Devriese LA, Brana I, Jankowska P, Posner M, Glisson B, Kong A, Hooftman L, Melief CJM MD,, Ferrarotto R. Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer. J Immunother Cancer. 2025 Sep 8;13(9):e012555. doi: 10.1136/jitc-2025-012555.

Reference Type DERIVED
PMID: 40921630 (View on PubMed)

Other Identifiers

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ISA101b-HN-01-17

Identifier Type: -

Identifier Source: org_study_id