Metastatic Castration-Resistant Prostate Cancer
Conditions
Keywords
PLK1, PLK Inhibitor, Onvansertib
Brief summary
The purpose of the phase 2 study is to determine whether Onvansertib is safe and tolerable in adult participants 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.
Interventions
Sponsors
Cardiff Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. Participants 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. Participant currently receiving abiraterone and prednisone for CRPC. 7. Participant has been on abiraterone for castration-sensitive prostate cancer (CSPC) or castration-resistant prostate cancer (CRPC). Participants 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. Participants who have received abiraterone for CRPC must have responded to abiraterone, defined by any decline in PSA, radiographic response, and/or clinical benefit after starting abiraterone. 8. Two rising PSA values separated by at least 1 week, one showing a rise of at least 0.3 ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy. 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 10. Participant has adequate bone marrow and organ function as shown by: * Absolute neutrophil count (ANC) ≥ 1.0 x 109/L * Platelets ≥ 100 x 10\^9/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 participants 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)
Exclusion criteria
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 initiation. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Disease Control at or Before 12 Weeks | Baseline up to Week 12 | Disease control was defined as lack of prostate-specific antigen (PSA) progression per Prostate Cancer Working Group 3 (PCWG3) criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absolute Change From Baseline in PSA at 12 Weeks | Baseline and Week 12 | PSA level was measured via blood sample. Mean and standard deviation change is reported. |
| Median Percentage Change From Baseline in PSA at 12 Weeks | Baseline and Week 12 | PSA level was measured via blood sample. Median, minimum and maximum change is reported. |
| Median Absolute Change From Baseline in PSA at 12 Weeks | Baseline and Week 12 | PSA level was measured via blood sample. Median, minimum and maximum change is reported. |
| Time to PSA Progression or Death | Up to approximately 100 weeks | Time to PSA progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any PSA progression per PCWG3 criteria: an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL. If a participant discontinued from the study without confirmed PSA progression or death, then they were censored at the last PSA laboratory date. Kaplan-Meier method was used. |
| Mean Percentage Change From Baseline in PSA at 12 Weeks | Baseline and Week 12 | PSA level was measured via blood sample. Mean and standard deviation change is reported. |
| Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks | Baseline up to Week 12 | Radiographic response is defined as the best overall response between Cycle 1 Day 1 and 12 weeks post-baseline being stable disease (SD) or better (partial response \[PR\] or complete response \[CR\]) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1): CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions. |
| Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks | Baseline up to Week 12 | Disease control was defined as lack of PSA progression per PCWG3 criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to approximately 27 months | Adverse events (AEs) are defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs with a start date after Cycle 1 Day 1. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 on a scale from Grade 1 (mild) to Grade 5 (death related to AE). |
| Number of Participants With DLTs | Arms A and B: up to one 21-day cycle; Arm C: up to two 14-day cycles | DLTs are defined as a CTCAE Grade 4 hematologic AE or CTCAE Grade ≥ 3 non-hematologic AE that is considered related to the study drug. |
| Time to Radiographic Progression or Death | Up to approximately 110 weeks | Time to radiographic progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any radiographic progression per PCWG3 criteria. If a participant discontinued from the study without confirmed radiographic progression or death, then they were censored at the last valid assessment date. |
Countries
United States
Participant flow
Recruitment details
A total of 72 participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC) were enrolled at 3 investigative sites in the United States between August 2018 and October 2023. Arm A was discontinued with Protocol Version 1.6 (08 Nov 2019). Any participants enrolled and were continuing treatment in Arm A had the opportunity to transition to Arm B (with a re-consent) at the start of their next cycle and at the discretion of the Investigator.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone On Day 1 of each cycle, onvansertib was administered PO, QD at a dose of 24 mg/m\^2 for 5 days (Day 1 through Day 5) out of a 21-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants also received abiraterone and prednisone. This arm was discontinued. | 24 |
| Arm B: Onvansertib + Abiraterone and Prednisone On Day 1 of each cycle, onvansertib was administered PO, QD at a dose of 24 mg/m\^2 for 5 days (Day 1 through Day 5) out of a 14-day cycle. Following DLT, the final recommended dose was reduced to 18 mg/m\^2 for 5 days (Day 1 through Day 5) out of a 14-day cycle as pre-specified in the protocol. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants also received abiraterone and prednisone. | 20 |
| Arm C: Onvansertib + Abiraterone and Prednisone On Day 1 of each cycle, onvansertib was administered PO, QD at a dose of 12 mg/m\^2 for 14 days (Day 1 through Day 14) out of a 21-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants also received abiraterone and prednisone. | 28 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Miscellaneous | 0 | 0 | 2 |
| Overall Study | Non-compliance With Study Drug | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 3 | 2 |
| Overall Study | Progressive Disease | 15 | 15 | 17 |
| Overall Study | Withdrawal of Informed Consent | 2 | 1 | 4 |
Baseline characteristics
| Characteristic | Arm A: Onvansertib + Abiraterone and Prednisone | Arm B: Onvansertib + Abiraterone and Prednisone | Arm C: Onvansertib + Abiraterone and Prednisone | Total |
|---|---|---|---|---|
| Age, Continuous | 70.7 years STANDARD_DEVIATION 7.44 | 71.3 years STANDARD_DEVIATION 8.39 | 69.4 years STANDARD_DEVIATION 9.12 | 70.4 years STANDARD_DEVIATION 8.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 16 Participants | 25 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 17 Participants | 23 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 20 Participants | 28 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 2 | 0 / 20 | 2 / 28 |
| other Total, other adverse events | 21 / 22 | 2 / 2 | 20 / 20 | 27 / 28 |
| serious Total, serious adverse events | 5 / 22 | 0 / 2 | 5 / 20 | 6 / 28 |
Outcome results
Primary
Percentage of Participants Achieving Disease Control at or Before 12 Weeks
Disease control was defined as lack of prostate-specific antigen (PSA) progression per Prostate Cancer Working Group 3 (PCWG3) criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval.
Time frame: Baseline up to Week 12
Population: Efficacy Population: comprises all participants who received at least 1 dose of onvansertib at the final recommended dose according to their arm assignments. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Disease Control at or Before 12 Weeks | 13.6 percentage of participants |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Disease Control at or Before 12 Weeks | 50.0 percentage of participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Disease Control at or Before 12 Weeks | 35.0 percentage of participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Disease Control at or Before 12 Weeks | 35.7 percentage of participants |
| Total | Percentage of Participants Achieving Disease Control at or Before 12 Weeks | 29.2 percentage of participants |
Secondary
Mean Absolute Change From Baseline in PSA at 12 Weeks
PSA level was measured via blood sample. Mean and standard deviation change is reported.
Time frame: Baseline and Week 12
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. If a participant did not have a Week 12 (+/- 3 days) PSA measure, then they are not included in this analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Mean Absolute Change From Baseline in PSA at 12 Weeks | 10.904 ng/mL | Standard Deviation 10.141 |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Mean Absolute Change From Baseline in PSA at 12 Weeks | 3.095 ng/mL | Standard Deviation 2.199 |
| Arm B: Onvansertib + Abiraterone and Prednisone | Mean Absolute Change From Baseline in PSA at 12 Weeks | 14.971 ng/mL | Standard Deviation 45.023 |
| Arm C: Onvansertib + Abiraterone and Prednisone | Mean Absolute Change From Baseline in PSA at 12 Weeks | 7.295 ng/mL | Standard Deviation 13.076 |
Secondary
Mean Percentage Change From Baseline in PSA at 12 Weeks
PSA level was measured via blood sample. Mean and standard deviation change is reported.
Time frame: Baseline and Week 12
Population: 100% Per-protocol (PP) Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. If a participant did not have a Week 12 (+/- 3 days) PSA measure, then they are not included in this analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Mean Percentage Change From Baseline in PSA at 12 Weeks | 84.330 percentage of PSA | Standard Deviation 52.545 |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Mean Percentage Change From Baseline in PSA at 12 Weeks | 67.064 percentage of PSA | Standard Deviation 50.35 |
| Arm B: Onvansertib + Abiraterone and Prednisone | Mean Percentage Change From Baseline in PSA at 12 Weeks | 42.661 percentage of PSA | Standard Deviation 60.818 |
| Arm C: Onvansertib + Abiraterone and Prednisone | Mean Percentage Change From Baseline in PSA at 12 Weeks | 77.675 percentage of PSA | Standard Deviation 94.611 |
Secondary
Median Absolute Change From Baseline in PSA at 12 Weeks
PSA level was measured via blood sample. Median, minimum and maximum change is reported.
Time frame: Baseline and Week 12
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. If a participant did not have a Week 12 (+/- 3 days) PSA measure, then they are not included in this analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Median Absolute Change From Baseline in PSA at 12 Weeks | 9.110 ng/mL |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Median Absolute Change From Baseline in PSA at 12 Weeks | 3.095 ng/mL |
| Arm B: Onvansertib + Abiraterone and Prednisone | Median Absolute Change From Baseline in PSA at 12 Weeks | 1.345 ng/mL |
| Arm C: Onvansertib + Abiraterone and Prednisone | Median Absolute Change From Baseline in PSA at 12 Weeks | 2.300 ng/mL |
Secondary
Median Percentage Change From Baseline in PSA at 12 Weeks
PSA level was measured via blood sample. Median, minimum and maximum change is reported.
Time frame: Baseline and Week 12
Population: 100% Per-protocol (PP) Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. If a participant did not have a Week 12 (+/- 3 days) PSA measure, then they are not included in this analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Median Percentage Change From Baseline in PSA at 12 Weeks | 94.814 percentage of PSA |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Median Percentage Change From Baseline in PSA at 12 Weeks | 67.064 percentage of PSA |
| Arm B: Onvansertib + Abiraterone and Prednisone | Median Percentage Change From Baseline in PSA at 12 Weeks | 25.828 percentage of PSA |
| Arm C: Onvansertib + Abiraterone and Prednisone | Median Percentage Change From Baseline in PSA at 12 Weeks | 54.630 percentage of PSA |
Secondary
Number of Participants With DLTs
DLTs are defined as a CTCAE Grade 4 hematologic AE or CTCAE Grade ≥ 3 non-hematologic AE that is considered related to the study drug.
Time frame: Arms A and B: up to one 21-day cycle; Arm C: up to two 14-day cycles
Population: Safety Population: comprises all participants who received any dose of onvansertib. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Number of Participants With DLTs | 4 Participants |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Number of Participants With DLTs | 0 Participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Number of Participants With DLTs | 4 Participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Number of Participants With DLTs | 3 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse events (AEs) are defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs with a start date after Cycle 1 Day 1. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 on a scale from Grade 1 (mild) to Grade 5 (death related to AE).
Time frame: Up to approximately 27 months
Population: Safety Population: comprises all participants who received any dose of onvansertib. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 22 Participants |
| Arm A: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with CTCAE Grade ≥3 | 12 Participants |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with CTCAE Grade ≥3 | 0 Participants |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 2 Participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 20 Participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with CTCAE Grade ≥3 | 11 Participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 27 Participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with CTCAE Grade ≥3 | 13 Participants |
Secondary
Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks
Radiographic response is defined as the best overall response between Cycle 1 Day 1 and 12 weeks post-baseline being stable disease (SD) or better (partial response \[PR\] or complete response \[CR\]) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1): CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Time frame: Baseline up to Week 12
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. Only participants with target or non-target lesions at Baseline and at least 1 post-baseline assessment are included. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks | 28.6 percentage of participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks | 62.5 percentage of participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks | 80.0 percentage of participants |
Secondary
Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks
Disease control was defined as lack of PSA progression per PCWG3 criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval.
Time frame: Baseline up to Week 12
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. Only participants with available data are included in the analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks | 13.3 percentage of participants |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks | 50.0 percentage of participants |
| Arm B: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks | 38.9 percentage of participants |
| Arm C: Onvansertib + Abiraterone and Prednisone | Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks | 36.0 percentage of participants |
Secondary
Time to PSA Progression or Death
Time to PSA progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any PSA progression per PCWG3 criteria: an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL. If a participant discontinued from the study without confirmed PSA progression or death, then they were censored at the last PSA laboratory date. Kaplan-Meier method was used.
Time frame: Up to approximately 100 weeks
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. Only participants with available data are included in the analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Time to PSA Progression or Death | 5.1 weeks |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Time to PSA Progression or Death | 10.5 weeks |
| Arm B: Onvansertib + Abiraterone and Prednisone | Time to PSA Progression or Death | 10.9 weeks |
| Arm C: Onvansertib + Abiraterone and Prednisone | Time to PSA Progression or Death | 9.0 weeks |
Secondary
Time to Radiographic Progression or Death
Time to radiographic progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any radiographic progression per PCWG3 criteria. If a participant discontinued from the study without confirmed radiographic progression or death, then they were censored at the last valid assessment date.
Time frame: Up to approximately 110 weeks
Population: 100% PP Population: consists of participants who have been administered 100% of the originally assigned study drugs in at least one full cycle, and without major protocol deviations. Only participants with target or non-target lesions at Baseline are included in the analysis. Arm A participants who transferred to Arm B and those who did not transfer are summarized separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Onvansertib + Abiraterone and Prednisone | Time to Radiographic Progression or Death | 12.0 weeks |
| Arm A to B: Onvansertib + Abiraterone and Prednisone | Time to Radiographic Progression or Death | NA weeks |
| Arm B: Onvansertib + Abiraterone and Prednisone | Time to Radiographic Progression or Death | 17.4 weeks |
| Arm C: Onvansertib + Abiraterone and Prednisone | Time to Radiographic Progression or Death | 57.0 weeks |