| Eligibility |
Inclusion Criteria:
- Histologically confirmed surgically resectable HNSCC oral cavity, hypopharynx,
oropharynx, and larynx
- Measurable disease defined as lesions that can be accurately measured by RECIST 1.1.
- Written informed consent and any locally-required authorization obtained from the
patient prior to performing any protocol-related procedures, including screening
evaluations
- Age >18 years at time of study entry or Adult male or female
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Body weight >30kg
- Life expectancy of at least 12 weeks
- Adequate normal organ and marrow function as defined below:
- Haemoglobin =9.0 g/dL
- Absolute neutrophil count (ANC) > 1500 per mm3
- Platelet count >75,000 per mm3
- Serum bilirubin =1.5 x institutional upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be =5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance
CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by
24-hour urine collection for determination of creatinine clearance:
Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine
(mg/dL)
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female
pre-menopausal patients. Women will be considered post-menopausal if they have been
amenorrheic for 12 months without an alternative medical cause. The following age-specific
requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and follicle-stimulating hormone levels in the
post-menopausal range for the institution or underwent surgical sterilization
(bilateral oophorectomy or hysterectomy).
- Women =50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical
sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Patient 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:
Involvement in the planning and/or conduct of the study Participation in another clinical
study with an investigational product during the last Concurrent enrolment in another
clinical study, unless it is an observational (non-interventional) clinical study or during
the follow-up period of an interventional study Any concurrent chemotherapy, IP, biologic,
or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
History of allogenic organ transplantation. Any unresolved toxicity NCI CTCAE Grade =2 from
previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory
values defined in the inclusion criteria
- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab or tremelimumab may be included only after consultation with
the Study Physician.
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first
dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory
bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of
diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome
[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis,
uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after
consultation with the study physician
- Patients with celiac disease controlled by diet alone Uncontrolled intercurrent
illness, including but not limited to, ongoing or active infection, symptomatic
congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions
associated with diarrhea, or psychiatric illness/social situations that would limit
compliance with study requirement, substantially increase risk of incurring AEs or
compromise the ability of the patient to give written informed consent History of
another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease History of active
primary immunodeficiency Active infection including tuberculosis (clinical evaluation
that includes clinical history, physical examination and radiographic findings, and TB
testing in line with local practice), hepatitis B (known positive HBV surface antigen
(HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2
antibodies). Patients with a past or resolved HBV infection (defined as the presence
of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
is negative for HCV RNA.
:Current or prior use of immunosuppressive medication within 14 days before the first dose
of durvalumab or tremelimumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
its equivalent Receipt of live attenuated vaccine within 30 days prior to the first
dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from screening
to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of
durvalumab + tremelimumab combination therapy.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
Prior treatment with an anti-PD-1, anti-PD-L1 (including durvalumab), anti-PD-L2,
anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
(including tremelimumab).
Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from screening
to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days
after the last dose of durvalumab monotherapy, whichever is the longer time period
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