Summary

Eligibility

1. Parts 1, 2, and 5: Participants with histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC) who are refractory to a novel antiandrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, or darolutamide) and have failed at least 1 (but not more than 2) taxane regimens including for metastatic hormone-sensitive prostate cancer (mHSPC) (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Note: A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Any NHT that has been administered and has been stopped for reasons other than progression will not be counted as an additional line of treatment.
2. Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.
3. Dose expansion phase: participants must not have had more than 2 NHTs and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-PD1, PARP inhibitors, radioligand therapies, sipuleucel-T, experimental agents) Note: Combinations are considered one systemic anti-cancer treatment.
4. Part 3: Participants with histologically or cytologically confirmed mCRPC who are refractory to a NHT (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen.
5. Parts 4A and 4B:
6. Participants with histologically or cytologically confirmed mCRPC who have received no or 1/2 prior NHT (given in any disease setting depending on the part), and no or 1 taxane (given for hormone sensitive prostate cancer).
7. Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable.
8. 4A: Participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible). Participants may have had exposure to up to 2 NHTs with a similar mechanism of action (apalutamide, enzalutamide or darolutamide) in the non-mCRPC and mCRPC setting.
9. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
10. All parts:
11. Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist.
12. Total serum testosterone <= 50 ng/dL or 1.7 nmol/L.
13. Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria:
14. PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
15. nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications.
16. appearance of 2 or more new lesions in bone scan.
17. Eastern Cooperative Oncology Group performance status of 0-1.
18. Adequate organ function, defined as follows:
19. Hematological function:
20. absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment).
21. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment).
22. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).
23. Renal function:
24. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation >= 30 ml/min/1.73 m^2.
25. Hepatic function:
26. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement).
27. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases).
28. Cardiac function:
29. left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available).
30. Baseline electrocardiogram (ECG) QTcF <= 470 msec (average of triplicate values).

Treatment Sites in Georgia

Winship Cancer Institute of Emory University

1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu