Phase II, Adjuvant Therapy for High-Risk HPV 16-Positive Oropharynx Cancer Patients With Durvalumab (MEDI4736) and MEDI0457 (INO-3112)
Phase II, Adjuvant Therapy for High-Risk HPV 16-Positive Oropharynx Cancer Patients With Durvalumab (MEDI4736) and MEDI0457 (INO-3112)
Combination immune checkpoint inhibitor and DNA vaccine will result in clearance of HPV DNA biomarkers (oral and/or plasma) for patients with persistent HPV-16 E6/E7 DNA (HPV biomarker) after treatment with curative intent.
Objectives:
Primary Objectives:
To determine whether combination immune checkpoint inhibitor, alone or together with a DNA vaccine will result in clearance of HPV biomarkers for patients at risk of disease progression.
Secondary Objective(s):
Exploratory Objective(s):
Inclusion Criteria:
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:
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.
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
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:
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:
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:
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.