An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2)

Study Overview
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Brief Summary
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This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm within the study will be 7 years.

Detailed Description
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This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Official Title
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CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) vs Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients With ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease

Conditions
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Breast Cancer, Early Breast Cancer

Intervention / Treatment
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* Drug: Camizestrant
* Drug: Tamoxifen
* Drug: Anastrozole
* Drug: Letrozole
* Drug: Exemestane
* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women and Men; ≥18 years at the time of screening (or per national guidelines) Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with absence of any evidence of metastatic disease as defined in the protocol. Completed adequate (definitive) locoregional therapy (surgery with or without radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant chemotherapy. Patients must be randomised within 12 months of definitive breast surgery. Patients may have received up to 12 weeks of endocrine therapy prior to randomisation. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Adequate organ and bone marrow function Exclusion Criteria: Inoperable locally advanced or metastatic breast cancer Pathological complete response following treatment with neoadjuvant therapy History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix or considered a very low risk of recurrence per investigator judgement) unless in complete remission with no therapy for a minimum of 5 years from the date of randomisation Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion precludes participation in the study or compliance  Known LVEF <50% with heart failure NYHA Grade ≥2. Mean resting QTcF interval > 480 ms at screening Concurrent exogenous reproductive hormone therapy or non topical hormonal therapy for non-cancer-related conditions Any concurrent anti-cancer treatment not specified in the protocol with the exception of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors ( eg, denosumab) Previous treatment with camizestrant, investigational SERDs/investigational ER targeting agents, or fulvestrant Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding. Patients with known hypersensitivity to active or inactive excipients of camizestrant or drugs with a similar chemical structure or class to camizestrant. In pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance to LHRH agonists that would preclude the patient from receiving any LHRH agonist.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomised in a 1:1 ratio to one of the following arms: • Arm A: Standard ET of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib • Arm B: Camizestrant ± abemaciclib
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib<br>standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib | Drug: Tamoxifen<br>* Tamoxifen. Comparator. Administered orally<br>Drug: Anastrozole<br>* Anastrozole. Comparator. Administered orally<br>Drug: Letrozole<br>* Letrozole. Comparator. Administered orally<br>Drug: Exemestane<br>* Exemestane. Comparator. Administered orally<br>Drug: Abemaciclib<br>* Abemaciclib adjuvant treatment Administered orally<br>|
| Experimental: Arm B: camizestrant ± abemaciclib<br>camizestrant ± abemaciclib | Drug: Camizestrant<br>* Camizestrant. Experimental. Administered orally<br>* Other names: AZD9833;Drug: Abemaciclib<br>* Abemaciclib adjuvant treatment Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive breast cancer-free survival (IBCFS) | IBCFS is defined as time from randomisation until date of first occurrence of: Invasive ipsilateral breast tumour recurrence Locoregional invasive breast cancer recurrence Distant recurrence Contralateral invasive breast cancer Death attributable to any cause. | Up to 14 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive disease-free survival (IDFS) | IDFS is defined as time from randomisation until date of first occurrence of one of the following events: Invasive ipsilateral breast tumor recurrence Locoregional invasive breast cancer recurrence Distant recurrence Contralateral invasive breast cancer Second primary non-breast invasive cancer Death attributable to any cause. | Up to 14 years | 
| Distant relapse-free survival (DRFS) | DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first. | Up to 14 years | 
| Overall survival (OS) | OS is defined as time from randomisation until death from any cause. | Up to 14 years | 
| Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0) |  | Until 28 days after the final dose of study treatment (up to 7 years) | 
| Proportion of time on study treatment with high side-effect burden as measured by the PGI-TT. |  | Until 28 days after the final dose of study treatment (up to 7 years) | 
| Change from baseline and time to deterioration of health-related quality of life as measured by the 2 global QoL items from the EORTC IL-311 |  | Until 28 days after the final dose of study treatment (up to 7 years) | 
| Pharmacokinetics (PK) | Plasma concentrations of camizestrant pre-dose (trough concentration) | Until 6 months from treatment start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER+, HER2-, breast cancer