Metastatic Breast Cancer, Locally Advanced Breast Cancer, Breast Cancer
Conditions
Keywords
Metastatic Breast Cancer, Advanced Breast Cancer, Breast Cancer, HR Positive, HER2-Negative
Brief summary
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.
Interventions
DRUGSamuraciclib
Samuraciclib tablet by mouth once a day
DRUGFulvestrant
Injection administered monthly (i.e., every 4 weeks), plus additional dose at Cycle 1 Day 15
Sponsors
Pfizer
Carrick Therapeutics Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Response (CBR) | From randomization until Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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) | 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. |
| Duration of Response (DOR) | 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) | 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. |
| Progression Free Survival (PFS) | 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) | 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. |
| Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 | From first dose of any study intervention through 28 days after the last dose of any study intervention | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. |
| 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) | — |
Countries
Hungary, Mexico, Spain, Turkey (Türkiye), United States
Outcome results
None listed