A randomized, double-blind, Phase III Study of AZD9833 plus CDK4/6 inhibitor (palbociclib or abemaciclib) in patients with metastatic breast cancer with detectable ESR1 mutation

SERENA-6: A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor (Palbociclib or Abemaciclib) vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole) + CDK4/6 Inhibitor in HR+/HER2- MBC Patients with Detectable ESR1 Mutation Without Disease Progression During 1L Treatment with Aromatase Inhibitor + CDK4/6 Inhibitor - SERENA-6

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-000546-17-ES

Enrollment

300

Registered

2021-07-13

Start date

2021-09-23

Completion date

Unknown

Last updated

2021-10-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Estrogen Receptor-Positive, HER-2 negative Advanced Breast Cancer MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864

Interventions

Product Name: AZD9833 - 25 mg Pharmaceutical Form: Film-coated tablet INN or Proposed INN: not yet available CAS Number: 2222844-89-3 Current Sponsor code: AZD9833 Concentration unit: mg milligram(s)

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent. • Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results. • Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib or abemaciclib) ± LHRH as the initial endocrine based treatment for advanced disease • Eastern Cooperative Oncology Group performance status of 0 or 1. • ESR1m positive detected by central testing of ctDNA • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. • Adequate organ and marrow function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120

Exclusion criteria

Exclusion criteria: • Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term. • Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. • Any evidence of severe or uncontrolled systemic diseases which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. • Patient with known or family history of severe heart disease • Previous treatment with AZD9833, investigational SERDs or fulvestrant. • Currently pregnant (confirmed with positive pregnancy test) or breastfeeding. • Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor and/or AI treatment.

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (approximately 2 years).;Main Objective: To demonstrate superiority of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of PFS in the FAS;Primary end point(s): Progression-free survival (PFS) is defined as the time from randomisation until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.;Secondary Objective: To demonstrate superiority of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of PFS2, OS and chemotherapy free survival in the FAS To estimate the effectiveness of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of : -ORR in patients with measurable disease at baseline -CBR24,Time to First and Second Subsequent Treatment in the FAS To assess breast and arm symptoms, pain, and physical functioning in participants treated with AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration To assess the safety and tolerability of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor in participants with advanced HR+/ HER2-negative BC	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (approximately 2 years).;Main Objective: To demonstrate superiority of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of PFS in the FAS;Primary end point(s): Progression-free survival (PFS) is defined as the time from randomisation until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.;Secondary Objective: To demonstrate superiority of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of PFS2, OS and chemotherapy free survival in the FAS To estimate the effectiveness of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor by assessment of : -ORR in patients with measurable disease at baseline -CBR24,Time to First and Second Subsequent Treatment in the FAS To assess breast and arm symptoms, pain, and physical functioning in participants treated with AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration To assess the safety and tolerability of AZD9833 plus CDK4/6 inhibitor relative to AI plus CDK4/6 inhibitor in participants with advanced HR+/ HER2-negative BC

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Secondary

Measure	Time frame
Secondary end point(s): 1. Overall survival (OS) 2. Progression-free survival 2 (PFS2) 3. Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 4. Chemotherapy-free survival 5. Clinical benefit rate at 24 weeks (CBR24) 6. Time to first subsequent anti-cancer therapy (TFST) 7. Time to second subsequent therapy (TSST) 8. Time to deterioration (TTD) 9. Plasma concentration of AZD9833 at specified timepoints 10. Change from baseline in EORTC QLQ-C30 and EORTC QLQ-BR45 scales;Timepoint(s) of evaluation of this end point: 1. OS approximately 5 years 2. PFS2 approximately 3.5 years 3. ORR approximately 5 years 4. CFS approximately 5 years 5. CBR24 at least 23 weeks from randomisation for each patient 6. TFST approximately 5 years 7. TSST approximately 5 years 8. TTD approximately 5 years 9. PK = on day 15 for each patient 10. EORTC C30/BR23 approximately 5 years.	—

Measure

Time frame

Secondary end point(s): 1. Overall survival (OS) 2. Progression-free survival 2 (PFS2) 3. Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 4. Chemotherapy-free survival 5. Clinical benefit rate at 24 weeks (CBR24) 6. Time to first subsequent anti-cancer therapy (TFST) 7. Time to second subsequent therapy (TSST) 8. Time to deterioration (TTD) 9. Plasma concentration of AZD9833 at specified timepoints 10. Change from baseline in EORTC QLQ-C30 and EORTC QLQ-BR45 scales;Timepoint(s) of evaluation of this end point: 1. OS approximately 5 years 2. PFS2 approximately 3.5 years 3. ORR approximately 5 years 4. CFS approximately 5 years 5. CBR24 at least 23 weeks from randomisation for each patient 6. TFST approximately 5 years 7. TSST approximately 5 years 8. TTD approximately 5 years 9. PK = on day 15 for each patient 10. EORTC C30/BR23 approximately 5 years.

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Countries

Australia, Austria, Bulgaria, Canada, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Portugal, Russian Federation, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Contacts

Public ContactUnidad de Investigación Clínica

AstraZeneca Farmacéutica Spain, S.A.

informacionEECC-Spain@astrazeneca.com+34900200444

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026