Advanced Breast Cancer
Conditions
Keywords
Estrogen receptor (ER)-positive, Human epidermal growth factor receptor 2 (HER2)-negative, Cyclin-Dependent Kinase (CDK) 4 inhibitors, Pharmacokinetics, Anti-tumor activity, Selective Estrogen Receptor Degrader (SERD), Safety, Tolerability
Brief summary
A study to investigate camizestrant in combination with atirmociclib in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.
Detailed description
This is a Phase IIa, sequential assignment, non- randomized, open-label treatment study to determine the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of camizestrant in combination with atirmociclib. The single-arm study includes: * Screening period * Atirmociclib single dose period * Doublet intervention period * Post-treatment follow-up period
Interventions
DRUGCamizestrant
Camizestrant will be administered orally.
DRUGAtirmociclib
Atirmociclib will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Participants with advanced adenocarcinoma of the breast and must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease. * Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting investigational medicinal products. * Eastern cooperative oncology group (ECOG)/World Health Organization (WHO) performance status 0 to 1, and a minimum life expectancy of 12 weeks. * At least one lesion that is measurable and/or non-measurable, as per RECIST 1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray, or clinical examination. * Menopausal status * Pre-menopausal women must start GnRH agonist therapy at least 4 weeks before study treatment and continue throughout the study. * Post-menopausal women must meet one of these criteria: bilateral oophorectomy, age ≥60 years, age ≥50 years with ≥12 months amenorrhea and intact uterus without hormonal therapy, or age \<60 years with ≥12 months amenorrhea and post-menopausal hormone levels. * Histological or cytological confirmation of adenocarcinoma of the breast. * Participants of childbearing potential must agree to use one highly effective contraceptive measure. * Documentation of ER-positive tumor irrespective of progesterone receptor status. Main
Exclusion criteria
* A participant who has received 2 or more lines of CDK4/6 inhibitors in the advanced disease setting. * A participant who has received prior camizestrant or atirmociclib treatment in the advanced disease setting. * Patients previously treated with other next generation selective estrogen receptor degrader (SERDs) or other experimental ETs in the advanced disease setting. * Patients previously treated with other experimental cyclin-dependent kinase (CDK) inhibitors are not eligible. * Inability to swallow oral medications. * Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia). * Presence of life-threatening metastatic visceral disease. * Any evidence of severe or uncontrolled systemic diseases. * Contraindication to or known intolerance/hypersensitivity of/to camizestrant or atirmociclib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) and serious AEs | Up to Post-Treatment Follow up (Day 30 Post Dose) | To investigate the safety and tolerability of camizestrant in combination with atirmociclib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration observed (Cmax) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Time to reach maximum (peak) plasma concentration following drug administration (tmax) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Terminal elimination rate constant (λz) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Terminal elimination half-life (t½λz) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Apparent total body clearance (CL/F) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Apparent volume of distribution at steady state (Vss/F) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Apparent volume of distribution based on the terminal phase (Vz/F) | At pre-defined intervals from Day -1 to Day 57 | To characterize the PK profile and parameters of atirmociclib. |
| Maximum concentration observed at steady state (Cssmax) | At pre-defined intervals from Day -1 to Day 57 | To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
| Area under the curve from 0 to the end of dosing interval (AUC0-tau) | At pre-defined intervals from Day -1 to Day 57 | To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
| Area under the curve from 0 to the end of dosing interval at steady state (AUCss0-tau) | At pre-defined intervals from Day -1 to Day 57 | To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
| Time to reach maximum plasma concentration at steady state (tssmax) | At pre-defined intervals from Day -1 to Day 57 | To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
| Objective Response Rate (ORR) | Up to 2 years | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Duration of Response (DOR) | Up to 2 years | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Clinical Benefit Rate at 24 Weeks (CBR24) | At 24 weeks | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Percentage change in tumor size | Up to 2 years | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Progression Free Survival (PFS) | Up to 2 years | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Progression-free survival landmark 6 months (PFSLM6m) | At 6 months | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
| Progression-free survival landmark 12 months (PFSLM12m) | At 12 months | To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Countries
United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed