Study to Evaluate the Safety and Tolerability of Camizestrant in Combination With Atirmociclib in Women With Advanced Breast Cancer

Official title

A Phase IIa, Open-label Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Camizestrant in Combination With Atirmociclib in Participants With ER-positive, HER2-negative Advanced Breast Cancer (SERENA-1b)

Overview

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

• Drug Camizestrant
  Camizestrant will be administered orally.
• Drug Atirmociclib
  Atirmociclib will be administered orally.

Primary outcome measures

• Number of participants with adverse events (AEs) and serious AEs [Time frame: Up to Post-Treatment Follow up (Day 30 Post Dose)]

Secondary outcome measures (12)

• Maximum concentration observed (Cmax) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Area under plasma concentration-time curve from time 0 to infinity (AUCinf) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Time to reach maximum (peak) plasma concentration following drug administration (tmax) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Terminal elimination rate constant (λz) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Terminal elimination half-life (t½λz) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Apparent total body clearance (CL/F) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Apparent volume of distribution at steady state (Vss/F) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Apparent volume of distribution based on the terminal phase (Vz/F) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Maximum concentration observed at steady state (Cssmax) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Area under the curve from 0 to the end of dosing interval (AUC0-tau) [Time frame: At pre-defined intervals from Day -1 to Day 57]
• Area under the curve from 0 to the end of dosing interval at steady state (AUCss0-tau) [Time frame: At pre-defined intervals from Day -1 to Day 57]

Eligibility 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Research Site — St Louis
• Research Site — East Providence
• Research Site — Nashville

United Kingdom · 3 centers

• Research Site — Cambridge
• Research Site — London
• Research Site — Manchester

Identifiers

NCT: NCT07427394 · D853CC00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗