Prostate Cancer Clinical Trials

• Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.

• Age ≥18 years.

• Has locally advanced surgically non-appropriate (unresectable and/or metastatic) cSCC (Cohort 1)..

• Has metastatic CRPC (Cohort 2):

‣ Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.

⁃ Documented prostate cancer progression as documented by PSA progression according to PCWG3 criteria.

⁃ Surgically or medically castrated, with serum testosterone level \<50 ng/dL.

• Refractory or naïve to anti-PD-1 therapy (Cohort 1). There is no limit on the number of prior lines of therapy. NOTE: Detailed information regarding duration of prior anti-PD-1 therapy and the extent of progression at the time of anti-PD-1 therapy discontinuation will be collected.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).

• Cohort 1: measurable disease per the RECIST v1.1 or Measurable by mRECIST for skin cancer or Global Assessment or Papillary/Ulceration Response Assessment or Pathological Assessment or WHO Criteria for Response Assessment in Cutaneous Squamous Cell Carcinoma, as appropriate (Appendix 4).

• Adequate organ and marrow function as defined below within 28 days of study treatment initiation:

‣ Hemoglobin \>9.0 g/dL

⁃ Absolute neutrophil count ≥1500/mL

⁃ Platelets ≥100,000/mL

⁃ Total bilirubin ≤1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤3 × ULN.

⁃ AST/alanine transaminase ≤2.5 × institutional ULN. Transaminases up to 3 × ULN in the presence of liver metastases.

⁃ Serum creatinine ≤1.5 × ULN OR measured or calculated creatinine clearance (CrCl; glomerular filtration rate can also be used in place of creatinine or CrCl) ≥60 mL/min for participants with creatinine levels \>1.5 × institutional ULN (CrCl should be calculated per institutional standard).

⁃ Urine protein \<2+ or 24-hour urine protein quantification \<1.0 g

⁃ For participants not receiving therapeutic anticoagulation: international normalized ratio or activated partial thromboplastin time ≤1.5 × ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.

⁃ Albumin \>2.5 mg/dL.

• Participants must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); 4 weeks from radiation therapy; and at least 2 weeks from palliative radiotherapy.

• Prior treatment with anti-VEGF therapy is allowed (Cohort 1).

• Adequately controlled blood pressure with 0 or 1 antihypertensive medication (defined as blood pressure ≤150/100 mmHg at screening and no changes in antihypertensive medication within 7 days of Day 1 Cycle 1.

• Women of childbearing potential (WOCBP) should have a negative urine or serum pregnancy within 72 hours prior to study treatment initiation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• WOCBP must agree to use adequate contraception during the study treatment period and for 120 days after completion of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• Male participants of childbearing potential must agree to use adequate contraception during the study treatment period and for 120 days after completion of study treatment.