A Study of Samuraciclib in Combination With Fulvestrant in Metastatic or Locally Advanced Breast Cancer in Adult Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of samuraciclib in combination with fulvestrant versus fulvestrant alone in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.

Official Title
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An Open-label, Interventional, Multicenter, Randomized, Phase 2 Study of Fulvestrant With or Without Samuraciclib in Participants With Metastatic or Locally Advanced Hormone Receptor (HR) Positive and Human Epidermal Growth Factor Receptor (HER)2-Negative Breast Cancer (BC)

Conditions
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Metastatic Breast Cancer, Locally Advanced Breast Cancer, Breast Cancer

Intervention / Treatment
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* Drug: Samuraciclib
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of ER-positive, HER2-negative locally advanced or metastatic breast cancer. Documented objective disease progression while on or within 6 months after the end of the most recent therapy. Received prior AI in combination with a CDK4/6i as the last therapy Known TP53 mutation status. Participants must have measurable disease or bone only disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Pre/peri-menopausal participants must have commenced treatment with a luteinizing hormone-releasing hormone (LHRH) agonist at least 4 weeks prior to first dose of study intervention. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 with no deterioration over the past 2 weeks. Expected life expectancy of >12 weeks in the judgement of the treating investigator. Exclusion Criteria: Inflammatory breast cancer. Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment. Inadequate hepatic, renal, and bone marrow function. Clinically significant cardiovascular disease. Any current or prior central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease. Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Arm A<br>Participants will receive 360 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15. | Drug: Samuraciclib<br>* Samuraciclib tablet by mouth once a day<br>Drug: Fulvestrant<br>* Injection administered monthly (i.e., every 4 weeks), plus additional dose at Cycle 1 Day 15<br>* Other names: Faslodex;|
| Experimental: Arm B<br>Participants will receive 240 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15. | Drug: Samuraciclib<br>* Samuraciclib tablet by mouth once a day<br>Drug: Fulvestrant<br>* Injection administered monthly (i.e., every 4 weeks), plus additional dose at Cycle 1 Day 15<br>* Other names: Faslodex;|
| Experimental: Arm C<br>Participants will receive fulvestrant administered monthly, plus additional dose at Cycle 1 Day 15. | Drug: Fulvestrant<br>* Injection administered monthly (i.e., every 4 weeks), plus additional dose at Cycle 1 Day 15<br>* Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Response (CBR) | CBR is defined as the overall complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks according to RECIST version 1.1 recorded from randomization until disease progression, or death due to any cause. | From randomization until Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR defined as the proportion of participants who achieved a best overall Response (BOR) of CR or PR per RECIST Version 1.1 from randomization until disease progression, or death due to any cause. | Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | 
| Duration of Response (DOR) | DOR defined as the time from the date of first documentation of objective tumor response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | 
| Progression Free Survival (PFS) | PFS defined as the time from the date of randomization to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | Time from the date of first dose of study intervention until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | 
| Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. | From first dose of any study intervention through 28 days after the last dose of any study intervention | 
| Samuraciclib plasma exposure: Cmax |  | Day 1 of Cycles 2 and 3 (each cycle is 28 days) | 
| Samuraciclib plasma exposure: Ctrough |  | Cycle 1 Days 8 and 15; Day 1 of Cycles 2, 3, 4, 5, and 6; and within 28 days of last dose (each cycle is 28 days) | 
| Fulvestrant plasma exposure: Ctrough |  | Cycle 1 Days 8 and 15; Day 1 of Cycles 2, 3, 4, 5 and 6; and within 28 days of last dose (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Breast Cancer, Advanced Breast Cancer, Breast Cancer, HR Positive, HER2-Negative