Squamous Cell Carcinoma of the OropharynxPhase 2NCT03669718
A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC
A Phase 2 study testing ISA101b and Cemiplimab in people with Squamous Cell Carcinoma of the Oropharynx and HPV16 Positive, run by ISA Pharmaceuticals at 44 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Oropharynx, HPV16 Positive
- What is being tested?
- ISA101b and Cemiplimab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 44 sitesin 13 countries
- Study dates
- 30 Nov 2018to Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
44 sites in 13 countries.
44 sites in 13 countries
United States10 sites
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60208
University of Cincinnati Cancer Institute
Cincinnati, Ohio, 45069
City of Hope
Duarte, California, 91010
M. D. Anderson Cancer Center
Houston, Texas, 77030
ICAHN School of Medicine at Mount Sinai
New York, New York, 10029
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Providence Portland Medical Center
Portland, Oregon, 97213
Moores Cancer Center at the UC San Diego Health
San Diego, California, 92093
University of California San Francisco
San Francisco, California, 94115
Washington University School of Medicine
St Louis, Missouri, 63110
France5 sites
Centre Léon Bérard
Lyon
CHU La Timone
Marseille
Antoine Lacassagne Center
Nice
Gustave Roussy
Paris
Hopitaux Universitaires Pitié Salpêtrière Charles Foix
Paris
Italy5 sites
ASST Spedali Civili Brescia, Department of Medical Oncology
Brescia
Azienda Ospedaliera San Paolo Polo Universitario
Milan
Istituto Nazionale dei Tumori
Milan
National Cancer Institute - IRCCS "Fondazione G. Pascale"
Naples
National Cancer Institute Regina Elena, IRCCS
Rome
United Kingdom5 sites
Aberdeen Royal Infirmary
Aberdeen
The Royal Marsden NHS Foundation
Chelsea
Guy's Hospital
London
The Royal Marsden NHS Foundation Trust
Sutton
Beacon Centre Musgrove Park Hospital
Taunton
Spain4 sites
Hospital Clinic of Barcelona
Barcelona
Hospital Duran i Reynals - Institut Catala dOncologia ICO
Barcelona
Vall d'Hebron
Barcelona
Hospital Universitario Marqués de Valdecilla Santander
Santander
Hungary3 sites
Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz
Nyíregyháza
University of Pecs Department of Oncotherapy
Pécs
Hetenyi Geza Korhaz-Rendelointezet
Szolnok
Netherlands3 sites
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066CX
Radboud University Medical Center
Nijmegen
University Medical Center Utrecht
Utrecht, 3584 CX
Brazil2 sites
DFSATR/Oncologia D'Or
Brasília
Instituto do Cancer do Estado de Sao Paulo
São Paulo
Poland2 sites
Maria Sklodowska-Curie National Institute of Oncology
Gliwice
Swietokrzyskie Oncology Center Kielce
Kielce
About this study
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 Oropharyngeal Cancer (OPC)
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.
Read the detailed description
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 .
- Being tested
- ISA101b, Cemiplimab, Placebo
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISA101bBiological
Every 3 weeks for a total of 3 times
CemiplimabDrug
Every 3 weeks for up to 24 months
PlaceboOther
Every 3 weeks for a total of 3 times
| Study group | Role | What they receive |
|---|---|---|
| Active ISA101b and cemiplimab. | Experimental | ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months Receives: Biological: ISA101b; Drug: Cemiplimab |
| Placebo and cemiplimab | Placebo comparator | Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months Receives: Drug: Cemiplimab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Measured using RECIST 1.1
Measured: 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".
Measured: 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.
Measured: 25months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start30 Nov 2018
- Primary completionSep 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of the OropharynxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 194 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ISA Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Bonnie S. Glisson, MD, BS, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03669718
- Sponsor's protocol ID
- ISA101b-HN-01-17
- Status last verified
- Dec 2023
- First submitted
- 11 Aug 2018
- Last updated
- 29 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40921630
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Oropharyngeal Cancer (OPC)
- ClinicalTrials.gov ID
- NCT03669718
- Acronym / sponsor ID
- ISA101b-HN-01-17
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 194 participants (estimated)
- Lead sponsor
- ISA PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 30 Nov 2018 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 13 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active ISA101b and cemiplimab. | Experimental | Biological: ISA101b, Drug: CemiplimabISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months |
| Placebo and cemiplimab | Placebo comparator | Drug: Cemiplimab, Other: PlaceboPlacebo 3 times plus cemiplimab every 3 weeks for up to 24 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISA101bEvery 3 weeks for a total of 3 times | Biological | Active ISA101b and cemiplimab. |
| CemiplimabEvery 3 weeks for up to 24 months | Drug | Active ISA101b and cemiplimab., Placebo and cemiplimab |
| PlaceboEvery 3 weeks for a total of 3 times | Other | Placebo and cemiplimab |
Primary outcome
Overall Response Rate
Time frame: 25months
Measured using RECIST 1.1
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: 25 months
1 secondary outcome
Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab.
Time frame: 25months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2023.
- Derived from this study: PubMed 40921630Even 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bonnie S. Glisson, MD, BS principal investigator
M.D. Anderson Cancer Center
44 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ISA101b and Cemiplimab in people with Squamous Cell Carcinoma of the Oropharynx and HPV16 Positive, run by ISA Pharmaceuticals at 44 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, France, Italy, United Kingdom, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: 25months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03669718, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2023.