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

NCT03669718 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ISA101b-HN-01-17
• Study Type: interventional
• Target: 194
• Locations: 13 countries
• Sites: 44

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Oropharynx; HPV16 Positive

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate

  Measured using RECIST 1.1

  25months

• Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0 "Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0".

  25 months

Secondary Outcomes (1)

• Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab.

  25months

Study Arms (2)

Active ISA101b and cemiplimab.

EXPERIMENTAL

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

Biological: ISA101b; Drug: Cemiplimab

Placebo and cemiplimab

PLACEBO COMPARATOR

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

Drug: Cemiplimab; Other: Placebo

Interventions

ISA101b BIOLOGICAL

Every 3 weeks for a total of 3 times

Active ISA101b and cemiplimab.

Cemiplimab DRUG

Every 3 weeks for up to 24 months

Active ISA101b and cemiplimab.; Placebo and cemiplimab

Placebo OTHER

Every 3 weeks for a total of 3 times

Placebo and cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ISA Pharmaceuticals: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (44)

City of Hope

Duarte, California, 91010, United States

Location

Moores Cancer Center at the UC San Diego Health

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60208, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

ICAHN School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45069, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Hospital Antwerp

Antwerp, Belgium

Location

DFSATR/Oncologia D'Or

Brasília, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo

São Paulo, Brazil

Location

University Hospital Olomouc

Olomouc, Czechia

Location

Nemocnice na Bulovce

Prague, Czechia

Location

Centre Léon Bérard

Lyon, France

Location

CHU La Timone

Marseille, France

Location

Antoine Lacassagne Center

Nice, France

Location

Gustave Roussy

Paris, France

Location

Hopitaux Universitaires Pitié Salpêtrière Charles Foix

Paris, France

Location

Universitaetsklinikum Ulm

Ulm, Germany

Location

Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz

Nyíregyháza, Hungary

Location

University of Pecs Department of Oncotherapy

Pécs, Hungary

Location

Hetenyi Geza Korhaz-Rendelointezet

Szolnok, Hungary

Location

ASST Spedali Civili Brescia, Department of Medical Oncology

Brescia, Italy

Location

Azienda Ospedaliera San Paolo Polo Universitario

Milan, Italy

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

National Cancer Institute - IRCCS "Fondazione G. Pascale"

Naples, Italy

Location

National Cancer Institute Regina Elena, IRCCS

Rome, Italy

Location

Consultorio de Oncología Médica

Oaxaca City, Mexico

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066CX, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Maria Sklodowska-Curie National Institute of Oncology

Gliwice, Poland

Location

Swietokrzyskie Oncology Center Kielce

Kielce, Poland

Location

Hospital Clinic of Barcelona

Barcelona, Spain

Location

Hospital Duran i Reynals - Institut Catala dOncologia ICO

Barcelona, Spain

Location

Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Marqués de Valdecilla Santander

Santander, Spain

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

The Royal Marsden NHS Foundation

Chelsea, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

Location

Beacon Centre Musgrove Park Hospital

Taunton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40921630 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Bonnie S. Glisson, MD, BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2018
• First Posted: September 13, 2018
• Study Start: November 30, 2018
• Primary Completion: September 1, 2024
• Study Completion: June 1, 2025
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

PL (2); ES (4); GB (5); ME (1); CZ (2); BR (2); HU (3); US (10); IT (5); BE (1); FR (5); DE (1); NL (3)