Study to Evaluate the Safety and Tolerability of Camizestrant in Combination With Atirmociclib in Women With Advanced Breast Cancer (SERENA-1b)

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Camizestrant; Drug: Atirmociclib

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

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Not yet recruiting
    • Research Site
  • London, United Kingdom, EC1M6BQ
    • Not yet recruiting
    • Research Site
  • Manchester, United Kingdom, M20 4GJ
    • Not yet recruiting
    • Research Site
• United States
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Not yet recruiting
      • Research Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Not yet recruiting
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camizestrant + Atirmociclib; Participants will receive a single dose of atirmociclib on Day -1 followed by combination of camizestrant and atirmociclib from Day 1.	Drug: Camizestrant; Camizestrant will be administered orally.; Drug: Atirmociclib; Atirmociclib will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) and serious AEs	To investigate the safety and tolerability of camizestrant in combination with atirmociclib.	Up to Post-Treatment Follow up (Day 30 Post Dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration observed (Cmax)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Area under plasma concentration-time curve from time 0 to infinity (AUCinf)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Time to reach maximum (peak) plasma concentration following drug administration (tmax)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Terminal elimination rate constant (λz)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Terminal elimination half-life (t½λz)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Apparent total body clearance (CL/F)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Apparent volume of distribution at steady state (Vss/F)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Apparent volume of distribution based on the terminal phase (Vz/F)	To characterize the PK profile and parameters of atirmociclib.	At pre-defined intervals from Day -1 to Day 57
Maximum concentration observed at steady state (Cssmax)	To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other.	At pre-defined intervals from Day -1 to Day 57
Area under the curve from 0 to the end of dosing interval (AUC0-tau)	To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other.	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)	To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other.	At pre-defined intervals from Day -1 to Day 57
Time to reach maximum plasma concentration at steady state (tssmax)	To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other.	At pre-defined intervals from Day -1 to Day 57
Objective Response Rate (ORR)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	Up to 2 years
Duration of Response (DOR)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	Up to 2 years
Clinical Benefit Rate at 24 Weeks (CBR24)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	At 24 weeks
Percentage change in tumor size	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	Up to 2 years
Progression Free Survival (PFS)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	Up to 2 years
Progression-free survival landmark 6 months (PFSLM6m)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	At 6 months
Progression-free survival landmark 12 months (PFSLM12m)	To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib.	At 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2026
• Primary Completion (Estimated): December 3, 2027
• Study Completion (Estimated): December 3, 2027

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability; Anti-tumor activity; Selective Estrogen Receptor Degrader (SERD); Estrogen receptor (ER)-positive; Human epidermal growth factor receptor 2 (HER2)-negative; Cyclin-Dependent Kinase (CDK) 4 inhibitors
• Additional Relevant MeSH Terms: AZD9833
• Other Study ID Numbers: D853CC00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No