Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: ISA 101; Nivolumab
Intervention description: 100 mcg administered subcutaneously for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1.; 3 mg/kg administered by vein every 2 weeks beginning on Day 8 after the first vaccine dose.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Solid Tumors; HPV-16 Positive Incurable Solid Tumors; ISA101; HPV-16 vaccination; Nivolumab; BMS-936558; Opdivo

Summary:

      The goal of this clinical research study is to learn if nivolumab combined with ISA101 can
      help to control cancer that has spread. The safety of the study drugs will also be studied.

      This is an investigational study. ISA101 is not FDA approved or commercially available. It is
      currently being used for research purposes only. Nivolumab is FDA approved to treat certain
      types of melanoma in patients who no longer respond to other drugs. Combining ISA101 with
      nivolumab is investigational. The study doctor can explain how the study drugs are designed
      to work.

      Up to 28 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Written Informed Consent: a. Subjects must have signed and dated an IRB/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. b) Subjects must be willing and
             able to comply with scheduled visits, treatment schedule, laboratory tests and other
             requirements of the study.

          2. Target Population: a. Men and women >/= 18 years of age. b. Eastern Cooperative
             Oncology Group (ECOG) performance status of </= 1. c. 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.

          3. Target Population: Subjects can be treatment naïve 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.

          4. Target Population: d. Subjects must have measurable disease by CT or MRI per RECIST
             1.1 criteria; Radiographic Tumor Assessment performed within 28 days of study
             inclusion. e. Target lesions may be located in a previously irradiated field if there
             is documented (radiographic) disease progression in that site. f. 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. g.
             Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to
             start.

          5. Target Population: h. All baseline laboratory requirements will be assessed and should
             be obtained within -14 days of study registration. Screening laboratory values must
             meet the following criteria: i) WBCs >/= 2000/uL; ii) Neutrophils >/= 1500/uL; iii)
             Platelets >/= 100 x 10^3/uL; iv) Hemoglobin >/= 9.0 g/dL; v) Serum creatinine of </=
             1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula).
             Female CrCl= (140- age in years) x weight in kg x 0.85 72 x serum creatinine in mg/
             dL. Male CrCl= (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/
             dL; vi) AST </= 1.5X ULN; vii) ALT </= 1.5X ULN; viii) Total bilirubin </= ULN (except
             subjects with Gilbert Syndrome who must have total bilirubin <3.0 mg/dl).

          6. Age and Reproductive Status: a) Women of childbearing potential (WOCBP) must use
             method(s) of contraception for 30 days + 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. b) WOCBP must have a negative serum
             or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
             within 24 hours prior to the start of investigational product.

          7. Age and Reproductive Status: c) Women must not be breastfeeding. d) 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:

          1. Target Disease Exceptions: a. Subjects with active 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. b. Subjects with carcinomatous
             meningitis.

          2. Medical History and Concurrent Diseases: a. 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. b. 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.

          3. Medical History and Concurrent Diseases: c. Prior therapy with anti-PD-1, anti-PD-L1,
             anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other
             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
             d. Subjects with a history of interstitial lung disease. e. Other active malignancy
             requiring concurrent intervention. f. 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.

          4. Medical History and Concurrent Diseases: g. Subjects with toxicities attributed to
             prior anti-cancer therapy other than alopecia and fatigue that have not resolved to
             grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. h.
             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. i.
             Treatment with any investigational agent within 28 days of first administration of
             study treatment.

          5. Physical and Laboratory Test Findings: a) Known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). b)
             Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
             ribonucleic acid (HCV RNA) indicating acute or chronic infection.

          6. Allergies and Adverse Drug Reaction: a) History of severe hypersensitivity reactions
             to other monoclonal antibodies. b) History of allergy or intolerance (unacceptable
             adverse event) to study drugs components.

          7. Sex and Reproductive Status: a) WOCBP who are pregnant or breastfeeding. b) Women with
             a positive pregnancy test at enrollment or prior to administration of study medication

          8. Prohibited Treatments and/or Restricted Therapies: a) Ongoing or planned
             administration of anti-cancer therapies other than those specified in this study. b)
             Use of corticosteroids or other immunosuppressive medications as per Exclusion
             Criteria 2b.

          9. Other Exclusion Criteria: a) 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. b) Prisoners or
             subjects who are involuntarily incarcerated. c) Subjects who are compulsorily detained
             for treatment of either a psychiatric or physical (eg, infectious disease) illness.