| Eligibility |
Inclusion Criteria:
- Written informed consent to participate in the study according to the investigational
review board (IRB)
- Suspected or histologically/cytologically confirmed oropharyngeal squamous cell
carcinoma (OPSCC), stage II, III, or IVA (according to the American Joint Committee on
Cancer [AJCC] 7th edition), or patients with loco-regional recurrence from an OPSCC
primary, if time of recurrence is at least 6 months after completion of initial
curative intent treatment (surgery or radiotherapy +/- chemotherapy or cetuximab).
Patients with a suspected lesion may be enrolled and a baseline biopsy will be
obtained as part of the study. If squamous cell histology is not confirmed, patients
will be discontinued from the study
- Patients must have surgically resectable disease in the opinion of the treating
physician. For patients with a primary OPSCC, patients must be eligible for TORS
(transoral robotic surgery)
- Available tissue from prior biopsy (minimum of 10 unstained slides), or willing to
undergo core biopsy to obtain tumor material. Biopsy will be mandatory for patients
with recurrent disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count >= 100 x 10^9/L (> 100,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not
apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional
upper limit of normal
- Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula
- Patients with reproductive potential (e.g., females menopausal for less than 1 year
and not surgically sterilized) must practice two highly effective contraceptive
measures for the duration of study drug therapy and for at least 90 days after
completion of durvalumab monotherapy or for at least 180 days after completion of
durvalumab/tremelimumab combination therapy. Female patients of childbearing potential
must provide a negative pregnancy test (urine) prior to treatment initiation
- 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:
- Histology other than squamous cell carcinoma
- Primary site other than oropharynx
- Prior systemic therapy (chemotherapy, biologic, or immunotherapy) for the same OPSCC.
Prior chemotherapy, biologic therapy, and radiotherapy is allowed in patients with
loco-regional recurrent disease, if administered at least 6 months prior to study
enrolment
- Previous treatment with Anti-CTLA-4 including tremelimumab or PD1/PD-L1 inhibitor,
including durvalumab
- History of another primary malignancy except for: (i) OPSCC with loco-regional
recurrence after 6 months of curative-intent treatment and amenable to salvage
surgery; (ii) malignancy treated with curative intent and with no evidence of active
disease >= 2 years before the first dose of study drug and of low potential risk for
recurrence; (iii) non-melanoma, skin cancer or lentigo maligna; in situ cervical,
breast, prostate or bladder carcinoma
- Any concurrent anticancer therapy
- Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from a baseline
electrocardiogram using Fridericia's correction
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab or tremelimumab, 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, and single dose of
dexamethasone of up to 20 mg (or equivalent corticosteroid) administered prior to
diagnostic or baseline study biopsy of the oropharynx, as per institution standard of
care
- 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) or pneumonitis
- History of primary immunodeficiency
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, seizures, 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 or tremelimumab
- Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing two highly effective methods of birth
control
- Any medical or psychosocial condition that will interfere with evaluation of study
treatment or interpretation of patient safety or study results
- Known allergy or hypersensitivity to investigational product (IP) or any excipient
- Any unresolved grade 2 or higher toxicity from previous anti-cancer therapy
- Primary tumor not amenable to TORS
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