Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

PRIMARY OBJECTIVES:

I. To investigate the effect of durvalumab on local and systemic immune activation by HPV
status in patients with oral cavity and oropharynx head and neck squamous cell carcinoma
(HNSCC).

II. To examine the effects of durvalumab on systemic immune response to HPV and tumor
associated antigens.

III. To examine the effects of durvalumab on immune regulatory mechanisms. IV. To explore the
association between levels of immune-regulatory micro-ribonucleic acid (miR) in plasma and
saliva and immune response.

SECONDARY OBJECTIVES:

I. Investigate the effect of the treatment with durvalumab on the computed tomography (CT)
scan and positron emission tomography (PET) scan response.

II. Evaluate the safety of a short induction treatment with durvalumab.

OUTLINE:

Patients receive durvalumab intravenously (IV) over approximately 60 minutes on day 1.
Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or
unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab,
patients undergo surgery. Patients may receive an additional dose of durvalumab if time to
surgery is longer than 30 days.

After completion of study treatment, patients are followed up for 90 days.

Inclusion Criteria:

- Histologically or cytologically confirmed HNSCC of the oral cavity (OC; more than 90%
patients have HPV negative cancer) or oropharynx (about 60-80% of patient have HPV
positive cancer)

- Presence of radiologically documented disease; all radiology studies must be performed
within 28 days prior to registration

- Any stage, considered candidates for surgery and scheduled for surgery either by
robotic or by standard surgical technique

- Documentation of HPV tested by polymerase chain reaction (PCR)

- Willing to provide consent for an additional tissue biopsy for research purposes, to
allow a part of their surgical tumor tissue to be utilized for research (in case tumor
tissue has not already been saved in the tumor tissue bank), and to donate samples of
blood and saliva collected weekly through the treatment

- All patients must have provided informed consent for correlative studies

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Patients must have no prior exposure to immune-mediated therapy, including anti-
cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1 (PD-1),
anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2
antibodies, excluding therapeutic anticancer vaccines

- At least 1 lesion, not previously irradiated, that can be accurately measured at
baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have a
short axis >= 15 mm) with CT or magnetic resonance imaging (MRI) and that is suitable
for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 guidelines

- Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have
elapsed between any major surgery and date of registration, and that wound healing has
occurred

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelet count >= 100 x 10^9/L

- Hemoglobin >= 9.0 g/dL

- Serum bilirubin =< 1.5 x upper limit of normal (ULN) (institutional upper limit of
normal)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

- Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by
24-hour urine collection for determination of creatinine clearance

- Female subjects must either be of non-reproductive potential (ie, post-menopausal by
history: >= 60 years old and no menses for >= 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative serum pregnancy test upon study
entry

- In accordance with National Cancer Institute of Canada Clinical Trials Group (NCIC
CTG) policy, protocol treatment is to begin within 2 working days of patient
registration

- Written informed consent and any locally-required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA] in the United States of American
[USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject
prior to performing any protocol-related procedures, including screening evaluations

- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up

Exclusion Criteria:

- Participation in another clinical study with an investigational product during the
last 6 months (mo)

- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab

- Receipt of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy,
targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
investigational agent) within the last 6 mo

- Mean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated
from 3 electrocardiograms (ECGs) using Fridericia's correction

- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid

- Any unresolved toxicity (> Common Terminology Criteria for Adverse Events [CTCAE]
grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that
is not reasonably expected to be exacerbated by the investigational product may be
included (e.g., hearing loss, peripherally neuropathy)

- Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > grade 1

- Active or prior documented autoimmune disease within the past 2 years; NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded

- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)

- History of primary immunodeficiency

- History of allogeneic organ transplant

- History of hypersensitivity to durvalumab or any excipient

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent

- Known history of active tuberculosis

- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab

- Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control

- Patients with body weight <= 30 kg

- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results