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
This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.
Detailed description
This is a multiple cohort study, an initial dose escalation phase is designed to confirm the safe dose of samuraciclib in combination with elacestrant. A Safety Review Committee (SRC) will monitor the safety, tolerability, and PK data during this phase. Once ascertained, an expansion cohort will be opened to explore the efficacy of samuraciclib in combination with elacestrant.
Interventions
DRUGSamuraciclib
Samuraciclib capsules by mouth once a day
Elacestrant tablets by mouth once a day
Sponsors
Carrick Therapeutics Limited
Berlin-Chemie AG Menarini Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
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 and ESR1 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 |
|---|---|---|
| Phase 1b (Dose-finding) | From the date of first dose of any study intervention (Day 1 Cycle 1) and through 28 days after the last dose of any study intervention | Identification of Samuraciclib + Elacestrant combination, Phase 2, expansion dose level. Incidence and severity of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse events (NCI-CTCAE) v5.0. Safety will be assessed by monitoring treatment - emerged severe and dose limiting adverse events and clinically relevant changes in vital signs and clinical laboratory results |
| Phase 2 (Expansion) | From the date of first dose of any study intervention (Cycle 1 Day 1) 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) is defined as the time from the date of first dose of IMP (Cycle 1 Day 1) to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability) | From the date of first dose of any study intervention through 28 days after the last dose of any study intervention | Type, incidence, severity (as graded by CTCAE v5.0), seriousness and relationship to study medications of AEs and any laboratory abnormalities. Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. |
| Clinical Benefit Response (CBR) | From the date of first dose of any study intervention (Cycle 1 Day 1) to ≥ 24 weeks or until disease progression or death to any cause (assessed up to 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 enrolment until disease progression, or death due to any cause. |
| Overall response rate (ORR) | the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | ORR is defined as the proportion of participants with a reduction in tumor burden with CR or PR according to RECIST version 1.1. ORR will be estimated for participants who received at least 1 dose of IMP, had measurable disease at baseline and had a postbaseline tumor assessment. |
| Duration of Response (DOR) | From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | DOR is 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 |
| Best percent change in tumor size. | From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48) | Best percent change in tumor size is defined as the percentage change in the sum of the longest diameters of target lesions |
| Samuraciclib plasma exposure: Cmax | Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days) | Plasma concentration for Samuraciclib |
| Elacestrant exposure: Cmax | Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days) | Plasma concentrations for Elacestrant |
| Samuraciclib plasma exposure: Ctrough | Cycle 1 Day 2 and 15; Day 2 of Cycle 2; Day 1 of Cycles 3-6 and end of treatment within 28 days of last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)] | — |
| Elacestrant exposure: Ctrough | Cycle 1 Day 2 and Day 15; Cycle 2 Day 2 of Cycle 2 and Day 1 of Cycles 3-6 and at end of treatment within 28 days of the last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days) | — |
| Genotyping for ESR1 and TP53 mutations | Screening | Genotyping for ESR1 and TP53 mutations to evaluate correlations between ESR1 and TP53 mutations and efficacy/safety findings |
Countries
France, Spain, United Kingdom, United States
Outcome results
None listed