Phase I/Ib Study of Pembrolizumab With Vorinostat for Patients With Advanced Renal or Urothelial Cell Carcinoma

Subject Inclusion Criteria

In order to be eligible for participation in this trial, the subject must:

• Have one of the following diagnoses/conditions:
• Renal cell carcinoma - previously treated and progressive disease, locally advanced or metastatic
• Urothelial cell carcinoma - previously treated and progressive disease, locally advanced or metastatic
• Prostate cell carcinoma - progressive disease, locally advanced or metastatic disease (enrolling only at IUSCC and its affiliates). Patients with hormone-sensitive disease where ADT in combination with either docetaxel or abiraterone is indicated will not be eligible (i.e. patients with high burden disease).
• Be willing and able to provide written informed consent for the trial.
• Be 18 years of age or older on day of signing informed consent.
• Have measurable disease based on RECIST 1.1. for patients with solid malignancies or evaluable disease as assessed by bone scan and/or PET scan. Patients with advanced or metastatic prostate cancer can have either androgen-sensitive or castration-resistant disease.
• Have a performance status of 0-2 on the ECOG Performance Scale.
• Demonstrate adequate organ function. All screening labs should be performed within 10 days of treatment initiation.
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Subjects of childbearing potential should be willing to use 2 methods of contraception for the course of the study through 120 days after the last dose of study medication. Acceptable methods of birth control include: abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections). NOTE: Females are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (a woman who is ≥45 years of age and has not had menses for greater than 1 year).
• Male subjects without a previous vasectomy should agree to use an adequate method of contraception (i.e. abstinence, condom with spermicidal foam/gel/film/cream) starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Subjects with urothelial carcinoma must have received a prior platinum-based regimen in the metastatic setting or have signed consent for this study within 12 months of receiving a platinum-based regimen in the perioperative setting (neoadjuvant or adjuvant).
• Subjects with a history of diabetes mellitus must have HgbA1c level of <8.5% upon study entry.

Subject Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle 1 Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1 Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.