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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03669718
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : November 8, 2019
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
ISA Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Oropharynx HPV16 Positive Biological: ISA101b Drug: Cemiplimab Other: Placebo Phase 2

Detailed Description:
This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with platinum refractory (progression on or within 6 months of platinum therapy) 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 .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study of Cemiplimab Versus the Combination of Cemiplimab With ISA101b in the Treatment of Subjects With HPV16-Positive Platin-Resistant Oropharyngeal Cancer (OPC)
Actual Study Start Date : November 30, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2022

Arm Intervention/treatment
Experimental: Active ISA101b and cemiplimab.
ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months
Biological: ISA101b
Every 3 weeks for a total of 3 times

Drug: Cemiplimab
Every 3 weeks for up to 24 months

Placebo Comparator: Placebo and cemiplimab
Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months
Drug: Cemiplimab
Every 3 weeks for up to 24 months

Other: Placebo
Every 3 weeks for a total of 3 times

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 20-25months ]
    Measured using RECIST 1.1

  2. 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". [ Time Frame: 20-25 months ]

Secondary Outcome Measures :
  1. Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab. [ Time Frame: 20-25months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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, not amenable to any therapy with curative intent. Subjects with HPV-16 positive squamous cell carcinoma (SCC) of occult primary site, presenting with lymph node(s) in the neck, are also eligible.
  • HPV-16 genotyping will be performed by the specified central reference laboratory.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Tumor progression or recurrence within 6 months after the last dose of platinum-containing chemotherapy (up to 2 lines of prior chemotherapy) administered as adjuvant therapy or in the context of primary or recurrent disease.
  • 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 known active brain metastases or leptomeningeal metastases are not allowed.
  • 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 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.
  • Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03669718

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Contact: Sonja Visscher +31713322310

  Hide Study Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Erminia Massarelli, MD, PhD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Alain Algazi, MD         
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60208
Contact: Mark Agulnik, MD         
United States, Ohio
University of Cincinnati Cancer Institute Recruiting
Cincinnati, Ohio, United States, 45069
Contact: Muhammad Kashif Riaz, MD         
United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Daniel Zandberg, MD         
United States, Texas
M. D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Bonnie Glisson, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Rafael Santana-Davila, MD         
University Hospital Antwerp Recruiting
Antwerp, Belgium
Contact: Pol Specenier, MD         
Grand Hopital de Chaleroi Recruiting
Charleroi, Belgium
Contact: Christophe Lonchay, MD         
University Hospital Leuven Recruiting
Leuven, Belgium, 3000
Contact: Paul Clement, MD         
Nemocnice na Bulovce Recruiting
Prague, Czechia
Contact: Petra Holečková, MD         
Fondation Hospital Saint Joseph Not yet recruiting
Paris, France
Contact: Michel Gatineau, MD         
Gustave Roussy Recruiting
Paris, France
Contact: Caroline Even, MD         
Hopitaux Universitaires Pitié Salpêtrière Charles Foix Recruiting
Paris, France
Contact: Aurelien Gobert, MD         
University Hospital Recruiting
Bonn, Germany
Contact: Franz-Georg Bauernfeind, MD         
IKrankenhaus Nordwest gGmbH, nstitut für Klinisch-Onkologische Forschung Recruiting
Frankfurt, Germany
Contact: Salah-Eddin Al-Batran, MD         
University Hospital Leipzig Recruiting
Leipzig, Germany
Contact: Andreas Dietz, MD         
Universitaetsklinikum Ulm Recruiting
Ulm, Germany
Contact: Simon Laban, MD         
Magyar Honvédség Egészségügyi Központ Recruiting
Budapest, Hungary
Contact: Zsuzsanna Emília Pápai, MD         
Onkolgiai Klinika Recruiting
Debrecen, Hungary
Contact: Peter Arkosy, MD         
Petz Aladar Megyei Oktat Krhz Recruiting
Gyor, Hungary
Contact: Tamas Pinter, MD         
Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz Recruiting
Nyiregyhaza, Hungary
Contact: Jozsef Erfan, MD         
University of Pecs Department of Oncotherapy Recruiting
Pecs, Hungary
Contact: Laszlo Mangel, MD         
Hetenyi Geza Korhaz-Rendelointezet Recruiting
Szolnok, Hungary
Contact: Tibor Csoszi, MD         
Istituto Nazionale dei Tumori Recruiting
Milan, Italy
Contact: Lisa Licitra, MD         
UOC Oncologia Medica Ospedale di Sondrio Recruiting
Sondrio, Italy
Contact: Alessandro Bertolini, MD         
Azienda Sanitaria Universitaria Integrata di Udine Not yet recruiting
Udine, Italy
Contact: Ciro Rossetto, MD         
Antoni van Leeuwenhoek Ziekenhuis Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Jan Paul Boer de, MD         
Leiden University Hospital Recruiting
Leiden, Netherlands
Contact: Marije Slingerland, MD         
Radboud University Medical Center Recruiting
Nijmegen, Netherlands
Contact: Carla Herpen, van, MD         
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Lot Devriese, MD         
Hospital Clnic i Provincial de Barcelona Recruiting
Barcelona, Spain
Contact: Juan Grau, MD         
Hospital Duran i Reynals - Institut Catala dOncologia ICO Recruiting
Barcelona, Spain
Contact: Miren Taberna, MD         
Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Irene Brana, MD         
Hospital Clinico San Carlos Recruiting
Madrid, Spain
Contact: Pedro Perez Segura, MD         
Hospital Universitario La Paz Recruiting
Madrid, Spain
Contact: Beatriz Castelo Fernandez, MD         
The 12 de Octubre University Hospital Recruiting
Madrid, Spain
Contact: Juan Antonio Núñez Sobrino, MD         
Universitario Sanchinarro Recruiting
Madrid, Spain
Contact: Lisardo Ugidos de la Varga, MD         
Hospital Universitario Virgen de la Victoria Recruiting
Malaga, Spain
Contact: Jose Manuel Trigo Perez, MD         
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain
Contact: Elvira del Barco Morillo, MD         
Hospital Universitario Marqués de Valdecilla Santander Recruiting
Santander, Spain
Contact: Almudena Garcia Castano, MD         
United Kingdom
The Royal Marsden NHS Foundation Recruiting
Chelsea, United Kingdom
Contact: Kevin Harrington, MD         
Beacon Centre Musgrove Park Hospital Recruiting
Taunton, United Kingdom
Contact: Petra Jankowska, MD         
Sponsors and Collaborators
ISA Pharmaceuticals
Regeneron Pharmaceuticals
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Principal Investigator: Bonnie S. Glisson, MD, BS M.D. Anderson Cancer Center

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Responsible Party: ISA Pharmaceuticals Identifier: NCT03669718     History of Changes
Other Study ID Numbers: ISA101b-HN-01-17
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell