Nivolumab and Synthetic Long E6/E7 Peptides Vaccine HPV-01 in Treating Patients with Recurrent or Metastatic Incurable HPV-16-Positive Solid Tumors

Inclusion Criteria

• Subjects must have signed and dated an Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
• Subjects with histologically- or cytologically-documented incurable human papillomavirus (HPV)-16 positive solid tumors including oropharyngeal squamous cell carcinoma (OPSCC), cervical, vulvar, vaginal, anal, penile cancer; incurable HPV-16 solid tumors are defined as tumors which are not curable by salvage approaches including resection and/or re-irradiation; HPV-16 serotype will be assessed by Cervista assay
• Subjects can be treatment naive for metastatic or incurable locally advanced HPV-16 positive solid tumors or can have one prior line of treatment
• Patients are eligible upon progression after definitive local treatment (usually concurrent chemoradiation) if they are not candidates for salvage surgery or re-irradiation; patients are also eligible after progression on first line chemotherapy for recurrent disease
• Subjects must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria; radiographic tumor assessment performed within 28 days of study inclusion
• Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
• Subject entering the study will need to consent for mandatory biopsy at study entrance and as an optional procedure at week 11 and at progression for biomarker evaluation; biopsy should be excisional, incisional or core needle; fine needle aspiration is insufficient
• Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to start
• All baseline laboratory requirements will be assessed and should be obtained within -14 days of study registration
• White blood cells (WBCs) >= 2000/uL
• Neutrophils >= 1500/uL
• Platelets >= 100 x 10^3/uL
• Hemoglobin >= 9.0 g/dL
• Serum creatinine of =< 1.5 X upper limit of normal (ULN) or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula)
• Aspartate aminotransferase (AST) =< 1.5 X ULN
• Alanine aminotransferase (ALT) =< 1.5 X ULN
• Total bilirubin =< ULN (except subjects with Gilbert syndrome who must have total bilirubin < 3.0 mg/dl)
• Women of childbearing potential (WOCBP) must use method(s) of contraception for 30 days plus (+) 5 half-lives (60 days) of the study drugs; for a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required; highly effective birth control in this study is defined as a double barrier method; examples include a condom (with spermicide) in combination with a diaphragm, cervical cap, or intrauterine device (IUD); the individual methods of contraception should be determined in consultation with the investigator
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of investigational product
• Women must not be breastfeeding
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; the investigator shall review contraception methods and the time period that contraception must be followed; men that are sexually active with WOCBP must follow instructions for birth control for a period of 90 days plus the time required for the investigational drug to undergo 5 half-lives (60 days)

Exclusion Criteria

• Subjects with active central nervous system (CNS) metastases are excluded; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks
• Subjects with carcinomatous meningitis
• Subjects with active, known or suspected systemic autoimmune disease; subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start; inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Prior therapy with anti-programmed cell death protein 1 (PD-1), anti-programmed cell death1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Subjects with a history of interstitial lung disease
• Other active malignancy requiring concurrent intervention
• Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue that have not resolved to grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4) or baseline before administration of study drug
• Subjects who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment
• Treatment with any investigational agent within 28 days of first administration of study treatment
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
• History of severe hypersensitivity reactions to other monoclonal antibodies
• History of allergy or intolerance (unacceptable adverse event) to study drugs components
• WOCBP who are pregnant or breastfeeding
• Women with a positive pregnancy test at enrollment or prior to administration of study medication
• Ongoing or planned administration of anti-cancer therapies other than those specified in this study
• Use of corticosteroids or other immunosuppressive medications
• Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness