HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma

NCT04369937 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 19-082
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HPV-Related Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck Squamous Cell Carcinoma (HNSCC); HPV-16-associated HNSCC; ISA101b; Pembrolizumab; Cisplatin; Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) at 2 years

  The proportion 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).

  Up to 2 years

Secondary Outcomes (3)

• Adverse Events Related to Study Treatment

  Up to 3 years

• Progression-free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

Study Arms (1)

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.

Radiation: IMRT (Intensity Modulated Radiotherapy); Drug: Pembrolizumab; Drug: Cisplatin; Biological: ISA101b

Interventions

IMRT (Intensity Modulated Radiotherapy) RADIATION

Radiation therapy

IMRT + Pembrolizumab + Cisplatin + ISA101b

Pembrolizumab DRUG

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.

IMRT + Pembrolizumab + Cisplatin + ISA101b

Cisplatin DRUG

Chemotherapy

IMRT + Pembrolizumab + Cisplatin + ISA101b

ISA101b BIOLOGICAL

ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16.

Also known as: HPV-16 Vaccine

IMRT + Pembrolizumab + Cisplatin + ISA101b

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Dan Zandberg: lead
• Merck Sharp & Dohme LLC: collaborator
• ISA Pharmaceuticals: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy, Intensity-Modulated; pembrolizumab; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Dan P Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Head and Neck and Thyroid Cancer Disease Sections

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 30, 2020
• Study Start: July 6, 2020
• Primary Completion: March 12, 2025
• Study Completion: January 15, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)