The purpose of the phase 2 study is to determine whether Onvansertib given orally once daily
for 5 consecutive days every 14 or 21 days is safe and tolerable in adult patients with
Metastatic Castration-Resistant Prostate Cancer who have disease progression while receiving
abiraterone acetate (abiraterone) and prednisone therapy, and to observe the effects of
Onvansertib in combination with abiraterone and prednisone on disease control.
1. Males ≥ 18 years of age on the day of consenting to the study.
2. Ability to swallow the study drug as a whole tablet.
3. Histologically confirmed prostate adenocarcinoma without significant small-
cell/neuroendocrine or other variant histologies, with rising PSA and/or radiographic
progression in the setting of castration-level testosterone (< 50 ng/dL) indicating
mCRPC. Patients must have either undergone surgical castration or continue on GnRH
agonist/antagonist on the appropriate schedule throughout the study period.
4. Asymptomatic or minimally symptomatic disease.
5. Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI at any
time (past or present).
6. Subject currently receiving abiraterone and prednisone for CRPC.
7. Subject has been on abiraterone for castration-sensitive prostate cancer (CSPC) or
castration-resistant prostate cancer (CRPC). Subjects who have received abiraterone
for CSPC must have had a response to hormonal therapy, as defined by any decline in
PSA, radiographic response and/or clinical benefit after starting hormonal therapy.
Subjects who have received abiraterone for CRPC must have responded to abiraterone,
defined by any decline in PSA, radiographic response, and/or clinical benefit after
8. Two rising PSA values separated by at least 1 week, one showing a rise of at least 0.5
ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy.
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
10. Subject has adequate bone marrow and organ function as shown by:
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Serum creatinine ≤ 2 x the upper limit of normal (ULN)
- Total serum bilirubin ≤ 1.5 x ULN (in subjects with known Gilbert Syndrome, a
total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (or
≤ 5.0 x ULN if hepatic metastases are present)
1. Major surgery within 28 days prior to starting study drug or has not recovered from
major side effects of the surgery.
2. Rapidly progressive symptoms of mCRPC.
3. Acute neurological dysfunction as a result of bone metastasis.
4. Previously treated with enzalutamide or experimental therapies directed against
androgen receptor (ie, apalutamide).
5. Use of any chemotherapy, investigational agents, immunotherapy, or hormonal therapy
other than GnRH agonists within 28 days of the start of treatment on protocol.
Use of bone targeted agents including bisphosphonates and RANK ligand inhibitors is
allowed if on stable dose; Xgeva or Zometa cannot be started within 28 days of
initiating study therapy.
6. Systemic corticosteroids except as part of on label treatment prostate cancer
regimens. Note: Topical applications (eg, rash), inhaled sprays (eg, obstructive
airways diseases), eye drops or local injections (eg, intra-articular) are allowed.
7. Treatment with any of the drugs listed in Section 8.4.5 at the time of study treatment
8. Has received wide field radiotherapy (including therapeutic radioisotopes such as
radium 223) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to
starting study drug or has not recovered from side effects of such therapy.
9. New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or
any other uncontrolled cardiac condition, or hypertensive or metabolic condition.
10. Myocardial infarction in the previous 12 weeks (from the start of treatment)
11. QT interval with Fridericia's correction [QTcF] >470 milliseconds. The QTcF should be
calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of
potentially correctible causes of QT prolongation (e.g., medications, hypokalemia),
the triplicate ECG may be repeated once during screening and that result may be used
to determine eligibility.
12. Planned concomitant use of medications known to prolong the QT/QTc interval
13. Presence of risk factors for torsade de pointes, including family history of Long QT
Syndrome or uncorrected hypokalemia.