This study aims to enroll 50 patients (male and female, age 18+) who have intermediate risk
disease with histologically-confirmed head and neck squamous cell carcinoma 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 ISA101b vaccine which
will be initiated 2 weeks prior to cisplatin-IMRT, and one week prior to the first dose of
pembrolizumab. Vaccines will continue for 2 additional administrations at weeks 2 and 5, on
the same day as successive pembrolizumab infusions. 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).
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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).
