BACK

ERα degradation and antagonism

CompoundCamizestrant

Area under investigation

Advanced solid tumors, HR-positive/HER2-negative breast cancer

Scientific PillarTumor Drivers & Resistance Mechanisms

 

Loading......

SERENA-4 trial overview

Tumor

HR+/HER2- advanced/metastatic breast cancer, 1L

Trial Identifier

NCT04711252

Phase

III

Regimen

Camizestrant + palbociclib; anastrozole + palbociclib

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria1,2 are –

  • Female or male, aged ≥18 years, with diagnosis of ER+/HER2– BC
  • Pre-/peri-menopausal women or men if amenable to be treated with concomitant, approved LHRH agonists for the duration of the study
  • Either de novo Stage IV disease, or disease recurrence from early stage BC after adjuvant ET
  • Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease
  • Measurable disease as defined per RECIST 1.1 OR at least one lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by computerized tomography or MRI
  • ECOG PS: 0 or 1
  • Adequate organ and marrow function

 

References: 

1. Study NCT04711252. ClinicalTrials.gov website.

2. Im S‑A, et al. Poster presented at: ASCO Annual Meeting; June 4–8, 2021; Virtual. J. Clin. Oncol. 2021;39. Abs TPS1101.

Exclusion criteria

The key exclusion criteria1,2 are –

  • Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6i with disease recurrence while on or within 12 months of completing treatment
  • Advanced, symptomatic, visceral spread that are at risk of life-threatening complications in the short term
  • Known active uncontrolled or symptomatic central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease
  • Any clinically important and symptomatic heart disease
  • Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participation or that would jeopardize compliance with the protocol
  • Any concurrent anti-cancer treatment
  • Active infection including tuberculosis, HBV and HCV

Study Locator

Explore further trial details, understand eligibility criteria and speak to clinical trial navigators for the SERENA-4 trial via the Breast Cancer Study Locator website.

Visit Study Locator

SERENA-4 overview model

SERENA-4 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

Cancel Continue

SERENA-4 Study Modal

SERENA-4 trial overview

Take me to Study Locator

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

Cancel Continue

Target Overview

Estrogen receptor alpha (ERα) is expressed in about 70% of breast cancer cases.1 ERα activity is essential for ER+ breast cancers, and while they may respond well to anti-estrogen therapies, such as aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs),2 resistance can emerge.3

Selective estrogen receptor degraders (SERDs) antagonize ERα and target it for degradation.1

Compound Overview

Camizestrant is an investigational next generation, oral, nonsteroidal ERα antagonist and selective estrogen receptor degrader. The molecule is being clinically evaluated as a potential treatment for HR+, HER2- breast cancers.

Mechanism of Action

  • Mechanism of Action

Bidard FC et al. Poster presented at: San Antonio Breast Cancer Symposium (SABCS); December 7-10, 2021; San Antonio, TX.

References

1. Gombos A. Curr Opin Oncol. 2019;31(5):424-429. 2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet. 2005;365(9472):1687-1717. 3. Jeselsohn R, Buchwalter G, De Angelis C, et al. Nat Rev Clin Oncol. 2015;12(10):573-583.

 

Loading......

SERENA-4 trial overview

Tumor

HR+/HER2- advanced/metastatic breast cancer, 1L

Trial Identifier

NCT04711252

Phase

III

Regimen

Camizestrant + palbociclib; anastrozole + palbociclib

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria1,2 are –

  • Female or male, aged ≥18 years, with diagnosis of ER+/HER2– BC
  • Pre-/peri-menopausal women or men if amenable to be treated with concomitant, approved LHRH agonists for the duration of the study
  • Either de novo Stage IV disease, or disease recurrence from early stage BC after adjuvant ET
  • Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease
  • Measurable disease as defined per RECIST 1.1 OR at least one lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by computerized tomography or MRI
  • ECOG PS: 0 or 1
  • Adequate organ and marrow function

 

References: 

1. Study NCT04711252. ClinicalTrials.gov website.

2. Im S‑A, et al. Poster presented at: ASCO Annual Meeting; June 4–8, 2021; Virtual. J. Clin. Oncol. 2021;39. Abs TPS1101.

Exclusion criteria

The key exclusion criteria1,2 are –

  • Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6i with disease recurrence while on or within 12 months of completing treatment
  • Advanced, symptomatic, visceral spread that are at risk of life-threatening complications in the short term
  • Known active uncontrolled or symptomatic central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease
  • Any clinically important and symptomatic heart disease
  • Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participation or that would jeopardize compliance with the protocol
  • Any concurrent anti-cancer treatment
  • Active infection including tuberculosis, HBV and HCV

Study Locator

Explore further trial details, understand eligibility criteria and speak to clinical trial navigators for the SERENA-4 trial via the Breast Cancer Study Locator website.

Visit Study Locator

SERENA-4 overview model

SERENA-4 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

Cancel Continue

SERENA-4 Study Modal

SERENA-4 trial overview

Take me to Study Locator

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

Cancel Continue

Abbreviations

View full glossary

  • 1L

    first line

  • aBC

    advanced breast cancer (locally advanced [inoperable] or metastatic breast cancer)

  • AE

    adverse event

  • AI

    aromatase inhibitor

  • BC

    breast cancer

  • CBR

    clinical benefit rate

  • CBR24

    clinical benefit rate at 24 weeks

  • CDK4/6i

    cyclin-dependent kinase 4/6 inhibitor

  • CTCAE

    Common Terminology Criteria for Adverse Events

  • ctDNA

    circulating tumor DNA

  • DoR

    duration of response

  • DRFS

    distant relapse-free survival

  • eBC

    early breast cancer

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • ER

    estrogen receptor

  • ER+

    estrogen receptor positive

  • ERE

    estrogen response element

  • ERα

    estrogen receptor alpha

  • ESR1

    estrogen receptor 1

  • ESR1m

    estrogen receptor 1 mutation

  • ET

    endocrine therapy

  • HBV

    hepatitis B virus

  • HCV

    hepatitis C virus

  • HER2

    human epidermal growth factor receptor 2

  • HER2-

    human epidermal growth factor receptor 2 negative

  • HR

    hormone receptor

  • HRQoL

    health-related quality of life

  • IBCFS

    invasive breast cancer-free survival

  • LHRH

    luteinizing hormone-releasing hormone

  • MRI

    magnetic resonance imaging

  • OD

    once daily

  • OFS

    ovarian function suppression

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • pCR

    pathological complete response

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • PK

    pharmacokinetics

  • PRO

    patient-reported outcomes

  • QoL

    quality of life

  • R

    randomization

  • RECIST

    Response Evaluation Criteria in Solid Tumors

  • SAE

    serious adverse event

  • SERD

    selective estrogen receptor degrader

  • SERM

    selective estrogen receptor modulator

  • SoC

    standard of care

  • TEAE

    treatment emergent adverse event

  • TFST

    time to first subsequent therapy

  • TSST

    time to start of second subsequent therapy

  • TTC

    time to chemotherapy

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

This site is intended for US Healthcare Professionals.

Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
©2026 AstraZeneca. All rights reserved.