| Eligibility |
Inclusion Criteria:
- Written informed consent and any locally-required authorization (e.g., HIPAA in the
USA, EU Data Privacy Directive in the EU) obtained from the subject prior to
performing any protocol-related procedures, including screening Evaluations.
- Age > 18 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (amend based on
specific study)
- Locally advanced HNSCC, UICC stage III-IVB (oral cavity, oropharynx, hypopharynx,
supraglottic larynx)
- Histological confirmation of HNSCC (regardless if p16 positive or negative)
- Measureable CD8 density in provided archival tumor tissue
- Body weight >30kg
- Adequate normal organ and marrow function as defined: Haemoglobin = 9.0 g/dL; White
blood cells (WBC) = 3,000 per mm3; Platelet count >100,000 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 (ULN)
- Creatinine Clearance >40ml/min (calculated from serum creatinine or cystatin C,
alternatively 24h urine possible)
- 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).
- 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:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the
last 4 weeks
- 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
- Distant metastases
- Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy,
targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) of the
locally advanced HNSCC
- Any other concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment, except the induction chemotherapy in the protocol. Concurrent use of
hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy)
is acceptable
- Prior radiotherapy of HNSCC
- Radiotherapy to more than 30% of the bone marrow or with a wide field of radiation
within 4 weeks of the first dose of study drug
- Major surgical procedure of the current locally advanced HNSCC (as defined by the
Investigator). Note: Local surgery of isolated lesions for palliative intent is
acceptable.
- History of allogenic organ transplantation.
- 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 areata
- 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 (eg, intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- 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 or180 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 randomisation or treatment in a previous durvalumab and/or tremelimumab clinical
study regardless of treatment arm assignment.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
steroid treatment, or any evidence of clinically active interstitial lung disease.
- Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
- 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
- Known allergy or hypersensitivity to durvalumab, tremelimumab, cisplatin/carboplatin,
docetaxel or any excipient
- Cisplatin/carboplatin induced polyneuropathy or hearing disorder
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