Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
SERENA-6
A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study
3 other identifiers
interventional
315
22 countries
263
Brief Summary
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2021
Longer than P75 for phase_3
263 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 30, 2021
CompletedStudy Start
First participant enrolled
June 30, 2021
CompletedFirst Posted
Study publicly available on registry
July 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2028
ExpectedApril 21, 2026
April 1, 2026
4 years
June 30, 2021
April 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1)
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.
From randomization until the earlier of the progression event or death (approximately 2 years)
Secondary Outcomes (8)
Progression-free survival 2 (PFS2)
From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (approximately 3.5 years)
Overall survival (OS)
From randomization until the date of death due to any cause (approximately 5 years)
Chemotherapy free survival
From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 5 years)
Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1
From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (approximately 5 years)
Clinical benefit rate at 24 weeks (CBR24)
At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)
- +3 more secondary outcomes
Study Arms (2)
AZD9833 + palbociclib, abemaciclib or ribociclib
EXPERIMENTALThe patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily)
Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib
ACTIVE COMPARATORThe patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Interventions
Dosage formulation: abemaciclib tablets will be administered orally
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.
Dosage formulation: ribociclib tablets will be administered orally
Dosage formulation: AZD9833 tablets will be administered orally
Dosage formulation: AZD9833 placebo tablets will be administrated orally.
Dosage formulation: anastrozole tablets will be administered orally.
Dosage formulation: letrozole tablets will be administered orally.
Dosage formulation: anastrozole placebo tablets will be administrated orally.
Dosage formulation: letrozole placebo tablets will be administered orally.
Dosage formulation: palbociclib tablets/capsules will be administered orally
Eligibility Criteria
You may qualify if:
- INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they:
- Have advanced breast cancer that is not able to be treated with surgery or radiation;
- Have an ESR1 mutation in their cancer;
- Have breast cancer that is HR-positive and HER2-negative;
- Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking these drugs for at least 6 months;
- Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor;
- Are able to do their daily activities;
- Are at least 18.
- 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, abemaciclib or ribociclib) ± LHRH as the initial endocrine based treatment for advanced disease;
- Eastern Cooperative Oncology Group performance status of 0 or 1;
- ESR1m detected by central testing of ctDNA with Guardant360® CDx;
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
- Adequate organ and marrow function.
You may not qualify if:
- INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they:
- Had certain types of tumors in the past that may come back;
- Are currently taking any other treatments for their cancer or other conditions including hormone replacements, medications, or supplements that could interfere with the trial treatment;
- Have or have had any major health problem, infection, or recent surgery that could make it difficult or dangerous to participate in this trial.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (265)
Research Site
Phoenix, Arizona, 85054, United States
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Hot Springs, Arkansas, 71913, United States
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Little Rock, Arkansas, 72205, United States
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Long Beach, California, 90806, United States
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San Diego, California, 92123, United States
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Santa Rosa, California, 92805, United States
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Grand Junction, Colorado, 81501, United States
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Lone Tree, Colorado, 80124, United States
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Fort Myers, Florida, 33901, United States
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Jacksonville, Florida, 32224, United States
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Jacksonville, Florida, 32256, United States
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St. Petersburg, Florida, 33705, United States
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Atlanta, Georgia, 30318, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30342, United States
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Park Ridge, Illinois, 60068, United States
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Fort Wayne, Indiana, 46804, United States
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Indianapolis, Indiana, 46250, United States
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Baltimore, Maryland, 21202, United States
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Boston, Massachusetts, 02215, United States
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Fairhaven, Massachusetts, 02719, United States
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Foxborough, Massachusetts, 02035, United States
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Milford, Massachusetts, 01757, United States
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South Weymouth, Massachusetts, 02190, United States
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Detroit, Michigan, 48202, United States
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Grand Rapids, Michigan, 49503, United States
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Rochester, Minnesota, 55905, United States
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Oxford, Mississippi, 38655, United States
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Kansas City, Missouri, 64111, United States
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St Louis, Missouri, 63110, United States
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Billings, Montana, 59101, United States
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Omaha, Nebraska, 68130, United States
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Camden, New Jersey, 08103, United States
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Ridgewood, New Jersey, 07450, United States
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Brooklyn, New York, 11215, United States
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East Syracuse, New York, 13057, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10065, United States
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New York, New York, 11355, United States
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Shirley, New York, 11967, United States
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Goldsboro, North Carolina, 27534, United States
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Canton, Ohio, 44710, United States
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Cincinnati, Ohio, 45220, United States
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Columbus, Ohio, 43219, United States
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Portland, Oregon, 97213, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15213, United States
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York, Pennsylvania, 17403, United States
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Greenville, South Carolina, 29607, United States
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West Columbia, South Carolina, 29169, United States
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Knoxville, Tennessee, 37916, United States
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Memphis, Tennessee, 38120, United States
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Nashville, Tennessee, 37203, United States
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Bedford, Texas, 76022, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77024, United States
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Houston, Texas, 77030, United States
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Irving, Texas, 75063, United States
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Longview, Texas, 75601, United States
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San Antonio, Texas, 78240, United States
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Salt Lake City, Utah, 84106, United States
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Midlothian, Virginia, 23114, United States
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Norfolk, Virginia, 23502, United States
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Tacoma, Washington, 98405, United States
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Waukesha, Wisconsin, 53226, United States
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Birtinya, 4575, Australia
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Darlinghurst, 2010, Australia
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Graz, 8036, Austria
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Innsbruck, 6020, Austria
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Salzburg, 5020, Austria
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Vienna, 1130, Austria
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Namur, 5000, Belgium
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Haskovo, 6300, Bulgaria
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Panagyurishte, 4500, Bulgaria
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Pleven, 5804, Bulgaria
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Plovdiv, 4004, Bulgaria
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Sofia, 1303, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Calgary, Alberta, T2N 5G2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Lévis, Quebec, G6V 3Z1, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H2X 0C1, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Québec, Quebec, G1S 4L8, Canada
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Avignon, 84918, France
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Brest, 29200, France
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Clermont-Ferrand, 63050, France
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Dijon, 21079, France
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Limoges, 83000, France
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Lorient, 56322, France
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Lyon, 69373, France
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Marseille, 13273, France
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Metz-Tessy, 74370, France
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Nîmes, 30029, France
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Paris, 75248, France
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Rouen, 76021, France
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Saint-Cloud, 92210, France
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Saint-Herblain, 44805, France
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Toulouse, 31100, France
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Tours, 37000, France
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Vandœuvre-lès-Nancy, 54519, France
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Vantoux, 57070, France
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Villejuif, 94805, France
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Ansbach, 91522, Germany
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Aschaffenburg, 63739, Germany
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Augsburg, 86156, Germany
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Bonn, 53111, Germany
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Chemnitz, 09116, Germany
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Dresden, 01307, Germany
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Erlangen, 91054, Germany
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Essen, 45130, Germany
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Freiburg im Breisgau, 79110, Germany
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Immenstadt im Allgäu, 87509, Germany
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Koblenz, 56068, Germany
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Leipzig, 4103, Germany
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Mannheim, 68167, Germany
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München, 80634, Germany
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Paderborn, 33098, Germany
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Ratingen, 40878, Germany
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Ravensburg, 88212, Germany
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Regensburg, 93053, Germany
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Stade, 21680, Germany
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Tübingen, 72076, Germany
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Ulm, 89075, Germany
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Budapest, 1062, Hungary
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Budapest, 1122, Hungary
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Miskolc, 3526, Hungary
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Szekszárd, 7100, Hungary
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Szolnok, 5000, Hungary
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Zalaegerszeg, 8900, Hungary
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Beersheba, 8410101, Israel
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Haifa, 3109601, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 494142, Israel
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Ramat Gan, 5262000, Israel
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Bergamo, 24127, Italy
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Bologna, 40138, Italy
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Florence, 50134, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20141, Italy
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Misterbianco, 95045, Italy
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Naples, 80131, Italy
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Padova, 35128, Italy
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Roma, 00168, Italy
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Rozzano, 20089, Italy
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Kitaadachi-gun, 362-0806, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-8556, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 467-8602, Japan
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Niigata, 951-8566, Japan
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Osaka, 540-0006, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 003-0804, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 162-8655, Japan
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Takasaki-shi, 370-0829, Japan
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Takatsuki-shi, 569-8686, Japan
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Tsukuba, 305-8577, Japan
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Yokohama, 241-8515, Japan
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Drammen, 3004, Norway
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Oslo, 0450, Norway
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Bydgoszcz, 85-796, Poland
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Gdynia, 81-519, Poland
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Koszalin, 75-581, Poland
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Lodz, 90-302, Poland
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Poznan, 60-693, Poland
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Rzeszów, 35-001, Poland
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Tomaszów Mazowiecki, 97-200, Poland
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Warsaw, 02-781, Poland
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Guimarães, 4835-044, Portugal
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Lisbon, 1400-038, Portugal
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Lisbon, 1449-005, Portugal
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Lisbon, 1500-650, Portugal
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Lisbon, 1649-035, Portugal
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Loures, 2674-514, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-072, Portugal
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Porto, 4200-319, Portugal
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Vila Nova de Gaia, 4434-502, Portugal
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Moscow, 111123, Russia
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Moscow, 129090, Russia
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Moscow, 143423, Russia
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Nizhny Novgorod, 603126, Russia
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Podolsk, 142100, Russia
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Saint Petersburg, 194017, Russia
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Saint Petersburg, 197758, Russia
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Banská Bystrica, 974 01, Slovakia
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Bratislava, 833 01, Slovakia
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Košice, 041 91, Slovakia
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Michalovce, 07101, Slovakia
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Partizánske, 958 01, Slovakia
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Cheonan-si, 31151, South Korea
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Daegu, 42415, South Korea
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Goyang-si, 10408, South Korea
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Seongnam-si, 13620, South Korea
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Seongnam-si, 463-712, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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A Coruña, 15009, Spain
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Badalona, 08003, Spain
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Barcelona, 8035, Spain
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L'Hospitalet de Llobregat, 08908, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Murcia, 30008, Spain
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Sant Joan Despí, 08970, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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Bern, CH-3010, Switzerland
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Chur, CH-7000, Switzerland
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Winterthur, 8401, Switzerland
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Kaohsiung City, 833, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 710, Taiwan
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Taipei, 100, Taiwan
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Taipei, 110, Taiwan
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Taipei, 11259, Taiwan
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Taipei, 11490, Taiwan
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Taipei, 23561, Taiwan
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Taipei, Taiwan
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Taoyuan District, 333, Taiwan
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Adana, 01120, Turkey (Türkiye)
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Ankara, 06010, Turkey (Türkiye)
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Ankara, 06100, Turkey (Türkiye)
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Ankara, 06340, Turkey (Türkiye)
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Ankara, 06520, Turkey (Türkiye)
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Cordaleo, 35575, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Izmir, 35360, Turkey (Türkiye)
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Kadıkoy/Istanbul, 34722, Turkey (Türkiye)
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Kayseri, 38039, Turkey (Türkiye)
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Blackpool, FY3 8NR, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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London, SW3 6JJ, United Kingdom
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London, WC1N 3BG, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Newport, NP10 8FZ, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Portsmouth, PO6 3LY, United Kingdom
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Reading, RG2 9LH, United Kingdom
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Sheffield, S10 2SJ, United Kingdom
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Sutton, SM2 5PT, United Kingdom
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Taunton, TA1 5DA, United Kingdom
Related Publications (2)
Bidard FC, Mayer EL, Park YH, Janni W, Ma C, Cristofanilli M, Bianchini G, Kalinsky K, Iwata H, Chia S, Fasching PA, Brufsky A, Nowecki Z, Pascual J, Moreau L, Chen SC, Karadurmus N, Gal-Yam EN, Jung KH, Pernas S, McClain S, He W, Klinowska T, Huang-Bartlett C, Turner NC; SERENA-6 Study Group. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. N Engl J Med. 2025 Aug 7;393(6):569-580. doi: 10.1056/NEJMoa2502929. Epub 2025 Jun 1.
PMID: 40454637DERIVEDTurner N, Huang-Bartlett C, Kalinsky K, Cristofanilli M, Bianchini G, Chia S, Iwata H, Janni W, Ma CX, Mayer EL, Park YH, Fox S, Liu X, McClain S, Bidard FC. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023 Mar;19(8):559-573. doi: 10.2217/fon-2022-1196. Epub 2023 Apr 18.
PMID: 37070653DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 30, 2021
First Posted
July 16, 2021
Study Start
June 30, 2021
Primary Completion
June 30, 2025
Study Completion (Estimated)
September 1, 2028
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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.