HPV-Related Squamous Cell CarcinomaPhase 2NCT04369937
HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing IMRT (Intensity Modulated Radiotherapy), Pembrolizumab and Cisplatin in people with HPV-Related Squamous Cell Carcinoma and Head and Neck Squamous Cell Carcinoma, run by Dan Zandberg at 1 site in United States.
Trial summary
This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV-Related Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- IMRT (Intensity Modulated Radiotherapy), Pembrolizumab and Cisplatin
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2020to 9 Mar 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis, with a primary site being the oropharynx. Squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes - patients can enroll provided all other eligibility criteria are met.
- Patients must have intermediate risk disease.
- o Patients must meet one of the following criteria: Oropharynx: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following; ≥ AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form, Appendix A)
- T4 or N2c/N3 disease irrespective of tobacco exposure
- Unknown primary: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following
- ≥ N2a AND ≥ 10 pack-years tobacco exposure
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- N2c/N3 disease irrespective of tobacco exposure
- Patients should be considered not a candidate for curative-intent surgery with diagnosis of AJCC 7th edition Stage III, IVa, or IVb disease.
- Diagnostic simple palatine or lingual tonsillectomy is permitted, provided patient has RECIST-measurable nodal disease.
- Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred.
- Patients with simultaneous primaries are excluded, with the exception of patients with bilateral tonsil/base of tongue HPV+ cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma (resected or management deferred), who are eligible.
- No prior systemic (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer.
- Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed.
- Patients must be untreated with radiation above the clavicles.
- Patients with a history of curatively-treated non-HNSCC malignancy must be disease-free for at least 2 years except for excised and cured disease.
- The patient must undergo a mandatory research biopsy at baseline. There will be 2 other optional biopsies that the patient will be asked to consent to, the first is durking week 2 of pembrolizumab/ISA101b vaccination (prior to start of cisplatin-IMRT-this correlates to week (-)1), the second once will be during week 2 after the start of IMRT (this correlates to week 1).
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Age ≥ 18
- Patients must have measurable disease according to RECIST 1.1
- Patients must demonstrate adequate organ function
- Written informed consent must be obtained from all patients prior to study registration.
- Documentation of negative pregnancy within 10 days of treatment initiation.
Who cannot join
- Oral Cavity, Larynx, Hypopharynx or Nasopharyngeal primary site
- Current participation in or previous participation in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
- Prior treatment with anti-HPV agents except prevention HPV vaccines
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agents (pembrolizumab and ISA101b
- Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.
- Acquired Immune Deficiency Syndrome (AIDS).
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- Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- History of second malignancy within 2 years prior to Study Day 1 (except for excised and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial bladder cancer, or T1a or T1b prostate cancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA) since resection).
- Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- Acquired Immune Deficiency Syndrome (AIDS).
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- Significant pulmonary disease including pulmonary hypertension, history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
- History or current evidence of any other medical or psychiatric condition, therapy, or laboratory abnormality not in the best interest of the trial or subject to participate, per the treating investigator.
- Peripheral neuropathy ≥ Grade 2
- Significant cardiovascular disease.
- Significant thrombotic or embolic events within 3 months prior to Study Day 1.
- Major surgery within 6 weeks prior to Study Day 1 (subjects must have completely recovered from any previous surgery prior to Study Day 1). Biopsy, diagnostic tonsillectomy, airway tumor debulking or excisional lymph node biopsy do not constitute major surgery.
- Active infection requiring antibiotics or antifungals within 7 days prior to first dose of study drug.
- Significant electrolyte imbalance prior to enrollment (note that patients may be supplemented to achieve acceptable electrolyte values):
- Pregnant or breastfeeding (due to potential for teratogenic or abortifacient effects).
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Study Evaluating HPV-16 Vaccination (ISA101b) and Pembrolizumab Plus Cisplatin Chemoradiotherapy for "Intermediate Risk" HPV-16 Associated Head and Neck Squamous Cell Carcinoma (HNSCC)
This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma.
Read the detailed description
This study aims to enroll adult male and female patients who have intermediate risk disease with histologically-confirmed head and neck squamous cell carcinoma (HNSCC) with no evidence of distant metastasis. All patients will receive the same treatment and there is no active control group.
In this trial, patients will undergo biopsy followed by treatment with the ISA101b vaccine which targets human papillomavirus (HPV). The vaccine treatment will begin 2 weeks prior to cisplatin and Intensity-Modulated Radiation Therapy (cisplatin-IMRT) and one week prior to the first dose of pembrolizumab, an anti-cancer immunotherapy targeting PD-1. The vaccine will be administered 2 additional times at weeks 2 and 5. Pembrolizumab will be initiated 1 week prior to cisplatin-IMRT at the dose of 200 mg IV q3 weeks (+/- 3 days). Pembrolizumab will be continued concurrently through cisplatin-IMRT (weeks 3, 6 ), and continued for a 15 week maintenance period after completion of cisplatin-IMRT for a total pembrolizumab treatment period of 24 weeks (8 doses; 6 months).
The purpose of this study is to evaluate patient survival following this combination of treatments.
- Being tested
- IMRT (Intensity Modulated Radiotherapy), Pembrolizumab, Cisplatin, ISA101b
- Keywords
- Head and Neck Squamous Cell Carcinoma (HNSCC), HPV-16-associated HNSCC, ISA101b, Pembrolizumab, Cisplatin, Chemoradiotherapy
- 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.
IMRT (Intensity Modulated Radiotherapy)Radiation
Radiation therapy
PembrolizumabDrug
A potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2.
CisplatinDrug
Chemotherapy
ISA101bBiological
Also called HPV-16 Vaccine
ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16.
| Study group | Role | What they receive |
|---|---|---|
| IMRT + Pembrolizumab + Cisplatin + ISA101b | Experimental | IMRT (Intensity Modulated Radiotherapy) of 70 Gy in 35 fractions over 7 weeks (5 fractions per week).
Pembrolizumab will be administered at 200 mg (fixed dose) IV every 3 weeks (+/- 3 days), beginning beginning one week (week -1) prior to concurrent cisplatin-IMRT.
Cisplatin will be administered at 100 mg/m2 IV on days 1(Week 0) and 22 (Week 3).
ISA101b will be administered as three rounds of vaccination 3-4 weeks apart via two SC injections per vaccination round at 100ug/peptide, before pembrolizumab treatment. Vaccination #1 will be administered 1 week before pembrolizumab. Receives: Radiation: IMRT (Intensity Modulated Radiotherapy); Drug: Pembrolizumab; Drug: Cisplatin; Biological: ISA101b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) at 2 Years
The percentage of participants whose disease has to progressed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2 years. PFS will be calculated from treatment initiation to disease progression or death from any cause for 2 years. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: At 2 years
Secondary outcomes (1)
Serious Adverse Events Related to Study Treatment
Number of patients who experienced Serious Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 that are possibly, probably or definitely related to study treatment.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start6 Jul 2020
- Primary completion12 Mar 2025
- Study completion9 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HPV-Related Squamous Cell CarcinomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dan Zandberg
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, ISA Pharmaceuticals
- Responsible party
- Sponsor-investigator, Dan Zandberg, University of Pittsburgh Medical Center
- Investigators
- Dan P Zandberg, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369937
- Sponsor's protocol ID
- HCC 19-082
- Status last verified
- Apr 2026
- First submitted
- 27 Apr 2020
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating HPV-16 Vaccination (ISA101b) and Pembrolizumab Plus Cisplatin Chemoradiotherapy for "Intermediate Risk" HPV-16 Associated Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT04369937
- Acronym / sponsor ID
- HCC 19-082
- Keywords
- Head and Neck Squamous Cell Carcinoma (HNSCC), HPV-16-associated HNSCC, ISA101b, Pembrolizumab, Cisplatin, Chemoradiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Dan ZandbergUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, ISA Pharmaceuticals
- Study start
- 6 Jul 2020 (actual)
- Primary completion
- 12 Mar 2025 (actual)
- Study completion
- 9 Mar 2026 (actual)
- First posted
- 30 Apr 2020 (actual)
- Results
- Posted 13 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma.
Detailed description
This study aims to enroll adult male and female patients who have intermediate risk disease with histologically-confirmed head and neck squamous cell carcinoma (HNSCC) with no evidence of distant metastasis. All patients will receive the same treatment and there is no active control group.
In this trial, patients will undergo biopsy followed by treatment with the ISA101b vaccine which targets human papillomavirus (HPV). The vaccine treatment will begin 2 weeks prior to cisplatin and Intensity-Modulated Radiation Therapy (cisplatin-IMRT) and one week prior to the first dose of pembrolizumab, an anti-cancer immunotherapy targeting PD-1. The vaccine will be administered 2 additional times at weeks 2 and 5. Pembrolizumab will be initiated 1 week prior to cisplatin-IMRT at the dose of 200 mg IV q3 weeks (+/- 3 days). Pembrolizumab will be continued concurrently through cisplatin-IMRT (weeks 3, 6 ), and continued for a 15 week maintenance period after completion of cisplatin-IMRT for a total pembrolizumab treatment period of 24 weeks (8 doses; 6 months).
The purpose of this study is to evaluate patient survival following this combination of treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMRT + Pembrolizumab + Cisplatin + ISA101b | Experimental | Radiation: IMRT (Intensity Modulated Radiotherapy), Drug: Pembrolizumab, Drug: Cisplatin, Biological: ISA101bIMRT (Intensity Modulated Radiotherapy) of 70 Gy in 35 fractions over 7 weeks (5 fractions per week). Pembrolizumab will be administered at 200 mg (fixed dose) IV every 3 weeks (+/- 3 days), beginning beginning one week (week -1) prior to concurrent cisplatin-IMRT. Cisplatin will be administered at 100 mg/m2 IV on days 1(Week 0) and 22 (Week 3). ISA101b will be administered as three rounds of vaccination 3-4 weeks apart via two SC injections per vaccination round at 100ug/peptide, before pembrolizumab treatment. Vaccination #1 will be administered 1 week before pembrolizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis, with a primary site being the oropharynx. Squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes - patients can enroll provided all other eligibility criteria are met.
- Patients must have intermediate risk disease.
- o Patients must meet one of the following criteria: Oropharynx: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following; ≥ AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form, Appendix A)
- T4 or N2c/N3 disease irrespective of tobacco exposure
- Unknown primary: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following
Key exclusion criteria (21 listed)
- Oral Cavity, Larynx, Hypopharynx or Nasopharyngeal primary site
- Current participation in or previous participation in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
- Prior treatment with anti-HPV agents except prevention HPV vaccines
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agents (pembrolizumab and ISA101b
- Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.
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 |
|---|---|---|
| IMRT (Intensity Modulated Radiotherapy)Radiation therapy | Radiation | IMRT + Pembrolizumab + Cisplatin + ISA101b |
| PembrolizumabA potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2. | Drug | IMRT + Pembrolizumab + Cisplatin + ISA101b |
| CisplatinChemotherapy | Drug | IMRT + Pembrolizumab + Cisplatin + ISA101b |
| ISA101bAlso: HPV-16 VaccineISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16. | Biological | IMRT + Pembrolizumab + Cisplatin + ISA101b |
Primary outcome
Progression-free Survival (PFS) at 2 Years
Time frame: At 2 years
The percentage of participants whose disease has to progressed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2 years. PFS will be calculated from treatment initiation to disease progression or death from any cause for 2 years. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
1 secondary outcome
Serious Adverse Events Related to Study Treatment
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Dan P Zandberg, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IMRT (Intensity Modulated Radiotherapy), Pembrolizumab and Cisplatin in people with HPV-Related Squamous Cell Carcinoma and Head and Neck Squamous Cell Carcinoma, run by Dan Zandberg at 1 site in United States.
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 22 inclusion and 21 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: finished, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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?
Yes. Results are posted in the registry (first posted 13 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (PFS) at 2 Years (time frame: At 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 May 2026.