A Study of LY3295668 Erbumine in Participants With Breast Cancer That Has Spread to Other Parts of the Body

Study Overview
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Brief Summary
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The reason for this study is to determine the recommended phase 2 dose of the study drug LY3295668 erbumine in participants with breast cancer that has spread to other parts of the body.

Official Title
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A Phase 1b Study of Aurora A Kinase Inhibitor LY3295668 Erbumine in Monotherapy and Combination Therapy in Patients With Metastatic Breast Cancer Post CDK4/6 Inhibitor and Endocrine Therapy

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: LY3295668 Erbumine
* Drug: Endocrine therapy
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have hormone receptor positive and HER2 negative metastatic breast cancer Participant must have progressed on at least 1 line of endocrine therapy and 1 cyclin dependent kinase (CDK)4/6 inhibitor Participant must be able and willing to undergo mandatory tumor biopsy Participant must have normal organ function Participant must be able to swallow capsules Exclusion Criteria: Participant must not have had prior chemotherapy for mBC. Chemotherapy in the adjuvant/neoadjuvant setting is permitted Participant must not be currently enrolled in a clinical study Participant must not have another serious medical condition Participant must not have previously received an aurora kinase inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3295668 Erbumine Part A<br>LY3295668 erbumine administered orally (Part I). Approximately the first 10 participants enrolled in this arm will be administered midazolam. | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Midazolam<br>* Administered orally.<br>|
| Experimental: LY3295668 Erbumine Part B<br>LY3295668 erbumine administered orally (Part I). Approximately the first 10 participants enrolled in this arm will be administered midazolam. | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Midazolam<br>* Administered orally.<br>|
| Experimental: LY3295668 Erbumine + Endocrine Therapy Cohort 1<br>LY3295668 erbumine administered orally and endocrine therapy administered according to package label (Part II). | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Endocrine therapy<br>* Administered according to label instructions.<br>|
| Experimental: LY3295668 Erbumine + Endocrine Therapy Continuation Part C<br>LY3295668 erbumine administered orally and endocrine therapy administered according to package label (Part I). | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Endocrine therapy<br>* Administered according to label instructions.<br>|
| Experimental: LY3295668 Erbumine + Endocrine Therapy Switch Part D<br>LY3295668 erbumine administered orally and endocrine therapy administered according to package label (Part I). | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Endocrine therapy<br>* Administered according to label instructions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Reductions | Number of Participants with Dose Reductions | Baseline through Cycle 1 (28 Day Cycle) | 
| Part II: Number of Participants with Dose Limiting Toxicities (DLTs) | Part II: Number of Participants with DLTs | Baseline through Cycle 1 (28 Day Cycle) | 
| Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) | ORR | Baseline through Measured Progressive Disease (Estimated up to 23 Months) | 
| Duration of Response (DoR) | DoR | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated up to 23 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve CR, PR or SD With a Duration of At Least 6 Months | CBR | Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 23 Months) | 
| Progression-Free Survival (PFS) | PFS | Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 23 Months) | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3295668 | PK: AUC of LY3295668 | Predose Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: AUC of LY3295668 in Combination with Endocrine Therapy | PK: AUC of LY3295668 in Combination with Endocrine Therapy | Predose Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: AUC of Endocrine Therapy in Combination with LY3295668 | PK: AUC of Endocrine Therapy in Combination with LY3295668 | Predose Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: AUC of Midazolam | PK: AUC of Midazolam | Predose Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: AUC of Midazolam in Combination with LY3295668 | PK: AUC of Midazolam in Combination with LY3295668 | Predose Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aurora kinase A, kinase, aurora A, aurora kinase inhibitor, aurora kinase A inhibitor, kinase inhibitor, AURKA, AurA