| Eligibility |
Inclusion Criteria:
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in the
protocol. Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US, European Union [EU] obtained
from the patient/legal representative prior to performing any protocol-related
procedures, including screening evaluations.
- Men and women >or = 18 years at the time of study entry.
- Histologically or cytologically proven HPV16-positive or p16-positive oropharyngeal
squamous cell carcinoma.
- Eastern Cooperative Oncology Group (ECOG) 0-1 (Appendix A)
- Completion of primary therapy curative intent )surgery based or radiation based)
within the past year (date of last treatment + 1 year) OR newly diagnosed with a plan
for treatment with curative intent OR currently in primary treatment with curative
intent.
- Body weight or = 30kg
- Adequate organ function as follows:
- Absolute neutrophil count (ANC) > or = 1000/mm3
- Platelet count > or = 75 x 109/L(> or = 75,000 per mm3)
- Hemoglobin > or =9 g/dL
- Creatinine < or = 1.5 x institutional ULN or creatinine clearance (CrCI) > or =
40mL/min (if using Cockcroft-Gault formula below):
Female CrCI = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
Male CrCI= (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- Total Bilirubin < or = 1.5 x institutional ULN (except subjects with Gilbert Syndrome,
who can have total bilirubin < 3.0 mg/dL)
- AST(SGOT)/ALT(SGPT) < or = 2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be < or = 5x ULN
- Sexually active fertile men must use effective barrier birth control if their partners
are WOCBP for up to 217 days after the last dose of durvalumab.
- The effects of Durvalumab and MEDI0475 on the developing human fetus are unknown.
Women of child-bearing potential (WOCBP) and mes must agree to use at least one highly
effective method of contraception (hormonal or barrier method form of birth control;
abstinence) prior to study entry and for the duration of study participation and for
up to 217 days after the last dose of Durvalumab or MEDI0457.
- Should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she must inform her treating physician immediately.
- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
or equivalent units of HCG) within two weeks of screening.
- Women must not be breastfeeding
- 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 > or =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, 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.
- Patient understands the study regimen, its requirements, risks and discomforts and is
able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC
guidelines must be obtained before the performance of any protocol related procedures
that are not part of normal care.
- Subjects must be competent to report AEs, understand the drug dosing schedule and use
of medications to control AEs.
- Individuals of all races and ethnic groups are eligible for this trial. There is no
bias towards age, gender or race in the clinical trial outlined. This trial is open to
accrual of men and women who meet the inclusion/exclusion criteria outlined.
Exclusion Criteria:
- Participation in another clinical study with an investigational product during or
after primary therapy.
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
- Any unresolved toxicity NCI CTCAE Grade > or = 2 from previous anticancer therapy with
the exception of alopecia, vitiligo, and the laboratory values defined in inclusion
criteria.
- Patients with Grade > or = 2 neuropathy will be evaluated on a case-by-case basis
after consultation with Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with Study
Physician.
- 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.
- Subjects with a previous diagnosis of another primary malignancy are excluded with the
exception of
- Malignancy treated with curative intent and with no known active disease > or = 3
years and of low potential risk of recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease
- Thyroid or salivary cancer
- 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.
- 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 polyangitis, 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 study physician
- Patients with celiac disease controlled by diet alone
- Patients with stable, inactive rheumatoid arthritis
- 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 active primary immune deficiency
- Active infection including:
- tuberculosis (clinical evaluation that includes history, physical examination and
radiographic findings, and TB testing in line with local practice).
- Hepatitis B and or hepatitis C, (positive tests for hepatitis B surface antigen
or hepatitis C ribonucleic acid (RNA) or
- Patients with a past or resolved HBV infection (defined as the absence 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.
- human immunodeficiency virus (positive HIV 1/2 antibodies).
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
- Active systemic infection requiring therapy.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. 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 C. Corticosteroids 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 received live vaccine whilst receiving IP and up to
30 days after the last dose of IP.
- Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
- Use of anticoagulants and irreversible platelet inhibitors (e.g. clopidogrel,
prasugrel, ticagrelor, etc.) are not allowed. Low dose aspirin for cardiac prophylaxis
is allowed.
- Subjects are excluded if they have a condition requiring systemic treatment with
either corticosteroids (>10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration. Inhaled or
topical steroids and adrenal replacement doses > 10mg daily prednisone equivalents are
permitted in the absence of active autoimmune disease.
- Female patients who are pregnant or intend to become pregnant, breastfeeding or male
or female patients of reproductive potential who are not willing to employ effective
birth control from screening to 217 days after the last dose of durvalumab
monotherapy.
- Men with female partners (WOCBP) that are not willing to use contraception from
screening to 217 days after the last dose of durvalumab monotherapy.
- Unable to follow up per study schedule.
- Patient is 1 year or greater from completion of primary treatment.
- Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for
treatment of either psychiatric or physical (e.g. infectious disease) illness.
- Patients weighing <30kg at time of screening are to be excluded from enrollment.
- Prior therapy with an anti-PD-1, anti-PD-L1, including durvalumab anti-PDL-2, or
anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
- Judgement 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.
- Underlying medical conditions that, in the Investigator's opinion, will make the
administration of study drug hazardous or obscure the interpretation of toxicity or
adverse events. For example, prior symptomatic pneumonitis.
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