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.

Females with ER-positive HER2-negative ABC and who have experienced disease progression on a CDK4/6 inhibitor in combination with endocrine therapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.