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

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)

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.

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

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.