Abemaciclib Plus Darolutamide in Prostate Cancer That Has Spread After Initial Treatment

Study Overview
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Brief Summary
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The main purpose of this study is to learn more about the safety and tolerability of abemaciclib when given in combination with darolutamide to participants with prostate cancer that has spread after initial treatment. Participation may last up to 32 months.

Official Title
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A Phase 1b Study of Abemaciclib Plus Darolutamide in Men With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Darolutamide
* Drug: LHRH agonist/antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate. Metastatic castration-resistant prostate cancer evidenced by: Prostate-specific antigen (PSA) or radiographic progression despite castrate levels of testosterone At least 1 bone metastasis on bone scan and/or 1 soft tissue metastasis on computed tomography/magnetic resonance imaging (CT/MRI) Participants who have not undergone bilateral orchiectomy must continue luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists throughout the study. Have adequate organ function. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Exclusion Criteria: Prior treatment with cyclin-dependent kinase 4 and 6 (CDK4 and CDK6) inhibitors or darolutamide. Prior systemic therapy for metastatic castration-resistant prostate cancer(mCRPC) with cytotoxic chemotherapy, PARP inhibitors, novel hormonal agents (NHAs) (enzalutamide, apalutamide, and abiraterone), and radiopharmaceuticals. Serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. Clinically significant heart disease as evidenced by myocardial infarction, arterial thrombotic events, severe or unstable angina, or congestive heart failure (New York Heart Association Class III or IV) within 6 months of assignment to treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib + Darolutamide<br>Abemaciclib plus (+) darolutamide. Participants who have not undergone bilateral orchiectomy are required to continue background androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist/antagonist throughout the study. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Darolutamide<br>* Administered orally.<br>Drug: LHRH agonist/antagonist<br>* Physician's choice. Administered in accordance with the prescribing information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Administration Number of Participants with One or More SAEs Considered by the Investigator to be Related to Study Drug Administration | Date of first dose to study completion (approximately 32 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-Free Survival (rPFS) Assessed by Investigator rPFS Assessed by Investigator | rPFS Assessed by Investigator | Date of first dose to radiographic disease progression or death from any cause (approximately 32 months) | 
| Objective Response Rate (ORR): Percentage of Participants with Soft Tissue Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) | ORR: Percentage of Participants with Soft Tissue BOR of CR or PR | Date of first dose to radiographic disease progression or death from any cause (approximately 32 months) | 
| Duration of Response (DoR) | DOR | Date of first documented CR or PR to radiographic disease progression or death from any cause (approximately 32 months) | 
| Time to Prostate Specific Antigen (PSA) Progression | Time to PSA progression | Date of first dose to the first observation of PSA progression (approximately 32 months) | 
| Prostate Specific Antigen (PSA) Response Rate (PSA-RR): Percentage of Participants with a PSA Decrease of at Least 50% from Baseline | PSA-RR | Date of first dose to confirmed PSA progression (approximately 32 months) | 
| Pharmacokinetics (PK): Mean Concentrations of Abemaciclib and its Active Metabolite(s) | PK: Mean Concentrations of Abemaciclib and its Active Metabolite(s) | Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle = 28 days) | 
| Pharmacokinetics (PK): Mean Concentrations of Darolutamide and its Active Metabolite | PK: Mean Concentrations of Darolutamide and its Active Metabolite | Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle = 28 days) |