ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

PHASE 1b DOSE ESCALATION

Inclusion Criteria for Phase 1b Dose Escalation

Patients must meet all the following criteria to be enrolled in this study:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Life expectancy of at least 12 weeks
• Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
• Documented metastatic disease
• Must have undergone bilateral orchiectomy (surgical castration) or willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
• Serum testosterone 170 mmHg or diastolic BP > 105 mmHg at screening) despite 2 concomitant antihypertensive therapies
• QT interval corrected by the Fridericia correction formula (QTcF) > 500 msec on the screening ECG
• Active or symptomatic viral hepatitis or chronic liver disease
• History of unresolved adrenal dysfunction
• GI disorder that negatively affects absorption
• Required treatment with one of the prohibited concomitant medications;
• Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
• History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months prior to Day 1 of treatment, cerebral vascular accident or brain arteriovenous malformation
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or other cancer for which the patient has been disease-free for at least two years
• Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
• Patient unwilling or unable to comply with this study protocol

PHASE 1b: HEAVILY PRETREATED EXPANSION COHORT (HPEC)

Inclusion Criteria for Phase 1b HPEC

Patients must meet all the following criteria to be enrolled in this study:

• Age ≥ 18 years
• ECOG Performance Status 0-1
• Life expectancy of at least 12 weeks
• Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
• Documented metastatic disease
• At least 1 measurable lymph node per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
• Must have undergone bilateral orchiectomy (surgical castration) or willing to continue GnRH analog or antagonist (medical castration)
• Serum testosterone 170 mmHg or diastolic BP > 105 mmHg at screening) despite two concomitant antihypertensive therapies
• QTcF >500 msec on the screening ECG
• Active or symptomatic viral hepatitis or chronic liver disease
• History of unresolved adrenal dysfunction
• GI disorder that negatively affects absorption
• Required treatment with one of the prohibited concomitant medications
• Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
• History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months prior to day 1 of treatment, cerebral vascular accident or brain arteriovenous malformation
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or other cancer for which the patient has been disease-free for at least 2 years
• Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
• Patient unwil