Study of CPI-200 in Patients With Advanced Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-200 Via Intravenous Infusion in Patients With Advanced Solid Tumors

This is a prospective, open-label, single arm, non-randomized study of CPI-200 in patients with advanced tumors. CPI-200 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD)

Primary Objectives:

• To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-200 in patients with advanced tumors

Secondary Objectives:

• To evaluate the pharmacokinetics (PK) of CPI-200
• To evaluate clinical response and resolution of symptoms after CPI-200 treatment
• To characterize adverse events of CPI-200 in patients with advanced cancers

Up to 7 dose levels of CPI-200 will be tested using an accelerated titration method followed by a conventional 3 + 3 dose escalation study design. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intravenous injection of CPI-200 within 21 days:

• All Grade 4 or greater adverse events as determined by CTCAEv5 criteria, excluding toxicities clearly related to disease progression or inter-current illness
• Any Grade 3 or greater non-hematologic, non-dermatologic toxicity with the exception of Grade 3 nausea, vomiting or diarrhea if lasting less than 72 hours, alopecia, or Grade 3 fatigue if lasting less than 7 days as determined by CTCAEv5 criteria
• Grade 3 thrombocytopenia in the presence of bleeding
• Grade 3 or greater febrile neutropenia
• Any hematologic or non-hematologic adverse events or abnormal laboratory value(s) related to CPI-200 that result(s) in permanent study discontinuation of study treatment

Inclusion Criteria:

• Age >18 years
• Males and females
• Have a histologically or cytologically confirmed diagnosis of advanced solid tumor
• Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy
• Have an ECOG performance status of 0-1
• Have a life expectancy of at least 12 weeks (in the opinion of the investigator)
• Have adequate bone marrow reserve, liver and renal function
• Be reasonably recovered from preceding major surgery and no major surgery within 4 weeks prior to the start of Day 1 treatment
• Have a negative pregnancy test for females with child bearing age at screening and should not be breast feeding
• Be willing to abstain from sexual activity or practice physical barrier contraception from study entry to 3 months after the last day of treatment

Exclusion Criteria:

• Have peripheral sensory neuropathy of Grade 2 or greater at screening
• Have known hypersensitivity to chemotherapeutic agents
• Have thrombocytopenia with complications including hemorrhage or bleeding > Grade 2 that required medical intervention or any hemolytic condition or coagulation disorders that would make participation unsafe
• Have unresolved toxicity from previous treatment or previous investigational agents; excluding alopecia
• Received investigational agents or systemic anticancer agents (other than neurotoxic compounds) within 5 half lives or 28 days, whichever is shorter, prior to Day 1 of treatment
• Have signs or symptoms of end organ failure, major chronic illnesses other than cancer, or any severe concomitant conditions
• Have experienced any of the following within the 6-month period prior to screening: unstable angina, myocardial infarction or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%
• Have other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that would make the patient inappropriate for enrollment in this study
• Is pregnant or breast-feeding