Onvansertib in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer

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• Prostatic Neoplasms 6,353

Keywords

• PLK1
• PLK Inhibitor
• Onvansertib

Study arms

• Experimental
  Arm A: onvansertib + abiraterone and prednisone

  On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (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 will also receive abiraterone and prednisone. This arm was discontinued.

  Drug: Onvansertib · Drug: Abiraterone · Drug: Prednisone

• Experimental
  Arm B: onvansertib + abiraterone and prednisone

  On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (QD) at a dose of 24 mg/m\^2 for 5 days (Day 1 through Day 5) out of a 14-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants will also receive abiraterone and prednisone.

  Drug: Onvansertib · Drug: Abiraterone · Drug: Prednisone

• Experimental
  Arm C: onvansertib + abiraterone and prednisone

  On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (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 will also receive abiraterone and prednisone.

  Drug: Onvansertib · Drug: Abiraterone · Drug: Prednisone

Interventions

• DrugOnvansertib

  Onvansertib orally

  Also known as: PCM-075

• DrugAbiraterone

  Abiraterone orally

• DrugPrednisone

  Prednisone orally

Primary outcomes

1. 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

Secondary outcomes

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

Baseline characteristics

Publications

• Hagege A, Ambrosetti D, Boyer J, Bozec A, Doyen J, Chamorey E, He X, Bourget I, Rousset J, Saada E, Rastoin O, Parola J, Luciano F, Cao Y, Pages G, Dufies M. The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics. 2021 Sep 21;11(19):9571-9586. doi: 10.7150/thno.61711. eCollection 2021. PubMed 34646387 ↗

Study documents

• Study protocol · Nov 16, 2020
• Statistical analysis plan · May 23, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided