Immunotherapy Study of Evofosfamide in Combination With Ipilimumab

Inclusion Criteria

• •1. Patients must be willing and able to review, understand, and provide written consent before study enrollment
• •2. Patients must have either a histologically-confirmed metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck.
• •3. At least 18 years of age.
• •4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \> 60 %)
• •5. Measurable disease as defined by irRECIST. Patients with castrate-resistant prostate cancer can have measurable or evaluable disease. Patients with evaluable disease must have documented evidence of progressive disease as defined by any of the following:
• •1. Prostate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least \>/= 1.0 ng/mL;
• •2. New or increasing non-bone disease (RECIST 1.1 criteria);
• •3. Positive bone scan with 2 or more new lesions (PCWG3)
• •6. Adequate bone marrow function within 7 days and defined as:
• •1. White Blood Cell (WBC) ≥ 2500 cells/mm3
• •2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3cells
• •3. Absolute lymphocyte count (ALC) \>1000 cells/mm3
• •4. Hemoglobin ≥ 9 g/dL
• •5. Platelets (PLT) ≥ 75,000 cells/mm3
• •7. Acceptable renal function within 7 days defined as serum creatinine ≤ 2.0 times the institutional upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault formula).
• •8. Acceptable liver function within 7 days of day 1 of therapy defined as:
• •1. • Bilirubin ≤ 1.5 times institutional ULN; does not apply to patients diagnosed with Gilbert's syndrome.
• •2. • AST (SGOT) and ALT (SGPT) ≤ 3 times institutional ULN; if liver metastases are present, then ≤ 5 times ULN is allowed.
• •9. QTc interval of ≤ 450 msec (males) or 470 msec (females) calculated according to Fridericia's formula (QTc = QT/RR0.33; RR=RR interval)
• •10. Ability and availability to complete all prescribed biopsies (prior to the first evofosfamide dose and between day 15 of Cycle 2 and day 8 of Cycle 3)
• •11. At least 3 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, whichever is shorter, after targeted or biologic therapy excepting prior treatment with CTLA 4, PD-1, or PD-L1 blocking antibodies for which only a 2 week interval is required. Patients with prostate cancer, unless orchiectomy has been performed in them, may continue to receive androgen deprivation therapy (ADT), anti-androgen therapy or therapy that interferes with androgenic stimulation.
• •12. Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by CTCAE 4.0) or baseline level. Chronic stable grade 2 peripheral neuropathy secondary to neurotoxicity from prior therapies may be considered on a case by case basis by the Principal Investigator.
• •13. Female patients of childbearing age must have a negative serum HCG test within 7 days of study enrollment, unless prior hysterectomy or menopause (defined as age ≥ 55 years and twelve consecutive months without menstrual activity). Female patients should not become pregnant or breast-feed while on this study.
• •14. Sexually active male and female patients should use effective birth control (abstinence; hormonal or barrier method) for the duration of the study and at least 2 months from last dose.
• •8. History of risk factors for TdP, including family history of long QT syndrome.
• •9. Sustained systolic blood pressure (BP) \>140 mm Hg or \<90 mm Hg, diastolic BP \>100 mm Hg or \<60 mm Hg
• •10. Patients with newly diagnosed, uncontrolled and or untreated cancer; related central nervous system diseases are excluded.
• •11. Uncontrolled intercurrent illness, including, but not limited to, myocardial infarction within 6 months, unstable symptomatic ischemic heart disease, active uncontrolled infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements.
• •12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of day 1 of therapy.
• •13. Current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B and C cirrhosis, active pancreatitis or uncontrolled medical disease which in the opinion of the investigator could compromise assessment of efficacy.
• •14. Known human immunodeficiency virus (HIV)-positive unless on highly active antiretroviral therapy (HAART), and/or known Hepatitis B or C on treatment. Drug interactions between those agents and these experimental agents are wholly unknown (screening not required).
• •15. Known hypersensitivity to the components of study drugs, its analogs, or drugs of similar chemical or biologic composition.
• •16. Any live vaccine or non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
• •17. Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; or other investigational therapies.
• •18. Receiving medications that are strong inhibitors or inducers of CYP3A4 (Appendix D).
• •19. Use of any other concurrent investigational agents or anticancer agents including hormonal therapy, except in the case of prostate cancer patients who are being treated anti-androgen or bone targeting therapies.
• •20. Female patients who have been on hormone replacement therapy (HRT) for menopausal symptoms for a period of at least 2 months will not be excluded from the study provided the HRT regimen remains unchanged during the conduct of the study.