Determination of DLT was made during the first 28 days of treatment in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably, or definitely related to study drug. The MTD reflects the highest dose of ZEN003694 in combination with enzalutamide that did not cause a DLT in more than 1 of 6 patients. The RP2D is the recommended dose of ZEN003694 in combination with enzalutamide as determined in the dose confirmation phase of the study.

Participants in dose escalation

Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity of AEs was graded based on the National Cancer Institute's Common Terminology for Adverse Events (V4.03). A serious adverse event (SAE) was any AE that was: fatal; life-threatening; required in-patient hospitalization or prolonged an existing hospitalization; disabling or incapacitating; a congenital anomaly or birth defect; or any other important medical event.

All participants

The PSA response rate will be evaluated using PCWG2 criteria and defined as the proportion of patients with a PSA decline of at least 50%. Any change from baseline is confirmed by a second measurement at least 3 weeks later. PSA Response Rate will be evaluated using PCWG2 criteria and defined as following: Percentage change from baseline in PSA to 12 weeks post ZEN003694 dose. Only evaluate for patients with at least 12 weeks of treatment, the PSA assessment at 12 weeks (84 days +/-3 days) will be used; Maximum percent decrease in PSA from baseline that occurs at any point after treatment. Evaluable for all patients with post-baseline PSA. Arms will be combined to analyze efficacy in Cohort A and Cohort B.

Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.

Tumor response will be evaluated using the PCWG2 criteria. Patients with measurable disease will be evaluated for clinical benefit as determined by tumor response using RECIST v1.1. Patients with non-measurable bone disease will be evaluated for progression based on the presence of any new lesions by bone scans. Radiographic tumor evaluation will be performed at screening and every 3 cycles or more frequently as determined by the investigator. Using the tumor response that is determined by the investigator, best overall response will be determined using RECIST v1.1. Best overall response is defined as the best response recorded from the start of treatment until disease progression or study exit. Arms will be combined to analyze efficacy in Cohort A and Cohort B.

Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.

Overall progression free survival (PFS) is determined using the PCWG2 criteria. Overall PFS is measured from screening until the time that disease progression (radiographic progressive disease or clinical deterioration) or death is documented, whichever occurs first. Arms will be combined to analyze efficacy in Cohort A and Cohort B.

Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.

Radiographic progression-free survival (rPFS) is determined using the PCWG2 criteria to assess both soft-tissue and bone assessments. The rPFS is measured from screening until the time the first radiographic scan shows disease progression, or until the time of death, whichever occurs first. If radiographic disease progression is identified at the first on-treatment radiographic assessment at Cycle 3 Day 1 (8 weeks), radiographic progression must be confirmed by a second assessment 6 or more weeks later. Patients who do not progress radiographically or did not die prior to study exit are censored on the date of their last dose of ZEN003694. Arms will be combined to analyze efficacy in Cohort A and Cohort B.

Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.

AUC(0-24h) is defined as the area under the curve (plasma concentration of drug over a 24-hour time period).

All Evaluable Participants

Cmax is defined as the maximum or peak plasma concentration of drug.

All Evaluable Participants