Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors

Inclusion Criteria

• Patient is male or female aged ≥18 years.
• Patient provided signed and dated informed consent prior to initiation of any study procedures.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
• Patient has a predicted life expectancy of ≥3 months.
• Patient has a GFR of ≥30 mL/min/1.73 m^2.
• Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 × ULN, aspartate transaminase (AST), and /or alanine transaminase (ALT) ≤3 × ULN or ≤5 ×ULN, if due to liver involvement by tumor.
• Patient has adequate bone marrow function, as evidenced by hemoglobin ≥9.0 g/dL in the absence of transfusion within the previous 72 hours, platelet count ≥100×10^9cells/L, and absolute neutrophil count (ANC) ≥1.5×10^9 cells/L.
• Patient has no significant ischemic heart disease or myocardial infarction (MI) within 6 months before the first dose of CPX-POM and currently has adequate cardiac function, as evidenced by a left ventricular ejection fraction of >50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and corrected QT interval (QTc) <470 msec by Fridericia (QTcF). The eligibility of patients with ventricular pacemakers for whom the QT interval may not be accurately measurable will be determined on a case by-case basis by the Sponsor in consultation with the Medical Monitor.
• Patient and his/her partner agree to use adequate contraception after providing written informed consent through 3 months after the last dose of CPX-POM, as follows:
• For women: Negative pregnancy test during Screening and at Day 1 of each treatment cycle and compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile or postmenopausal.
• For men: Compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile. Men whose sexual partners are of child-bearing potential must agree to use 2 methods of contraception prior to study entry, during the study, and for 3 months after the treatment period.
• Patient is willing and able to participate in the study and comply with all study requirements.
• Patients must have histologically confirmed MIBC (≥T2, N0-N1, M0 per AJCC) pure or mixed histology urothelial carcinoma. Clinical node-positive (N1) patients are eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within the planned surgical LN dissection template.
• The initial TURBT that showed muscularis propria invasion should be within 8 weeks prior to beginning study therapy, when feasible. There must be adequate evaluable tumor burden in the tissue blocks (from initial or repeat TURBT with highest tumor content) to allow for analysis as determined by the local site pathologist.
• Patients must be ineligible for cisplatin-based chemotherapy due to any of the following:
• Creatinine clearance(CrCl) <60 mL/min with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• Hearing impaired ≥ Grade 2 by CTCAE criteria
• Neuropathy ≥ Grade 2 by CTCAE criteria
• Heart failure New York Heart Association (NYHA) ≥ III

Exclusion Criteria

Patients who meet any of the following exclusion criteria are not to be enrolled in the Expansion Cohort.

• Baseline GFR <30 mL/min/1.73 m^2.
• Women must not be pregnant or breastfeeding since we do not know the effects of CPX-POM on the fetus or breastfeeding child.
• Patients may not have concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with