ER-Positive HER2-Negative Breast CancerPhase 3SERENA-6NCT04964934
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
A Phase 3 study testing AZD9833, Anastrozole and Letrozole in people with ER-Positive HER2-Negative Breast Cancer, run by AstraZeneca at 264 sites in 23 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- ER-Positive HER2-Negative Breast Cancer
- What is being tested?
- AZD9833, Anastrozole and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 315 participants
- Where
- 264 sitesin 23 countries
- Study dates
- 30 Jun 2021to 1 Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- Are able to do their daily activities;
- Are at least 18.
- Full list of 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, 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.
Who cannot join
- 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.
- Full list of exclusion criteria:
- Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term;
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- 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.
Trial locations and contacts
264 sites in 23 countries.
264 sites in 23 countries
United States64 sites
Research Site
Atlanta, Georgia, 30318
Research Site
Atlanta, Georgia, 30322
Research Site
Atlanta, Georgia, 30342
Research Site
Baltimore, Maryland, 21202
Research Site
Bedford, Texas, 76022
Research Site
Billings, Montana, 59101
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Boston, Massachusetts, 02215
Research Site
Brooklyn, New York, 11215
Research Site
Camden, New Jersey, 08103
Research Site
Canton, Ohio, 44710
Research Site
Cincinnati, Ohio, 45220
Research Site
Columbus, Ohio, 43219
Research Site
Dallas, Texas, 75246
Research Site
Detroit, Michigan, 48202
Research Site
East Syracuse, New York, 13057
Research Site
Fairhaven, Massachusetts, 02719
Research Site
Fort Myers, Florida, 33901
Research Site
Fort Wayne, Indiana, 46804
Research Site
Foxborough, Massachusetts, 02035
Research Site
Goldsboro, North Carolina, 27534
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Grand Junction, Colorado, 81501
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Grand Rapids, Michigan, 49503
Research Site
Greenville, South Carolina, 29607
Research Site
Hot Springs, Arkansas, 71913
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Houston, Texas, 77024
Research Site
Houston, Texas, 77030
Research Site
Indianapolis, Indiana, 46250
Research Site
Jacksonville, Florida, 32224
Research Site
Jacksonville, Florida, 32256
Research Site
Kansas City, Missouri, 64111
Research Site
Knoxville, Tennessee, 37916
Research Site
Little Rock, Arkansas, 72205
Research Site
Lone Tree, Colorado, 80124
Research Site
Long Beach, California, 90806
Research Site
Longview, Texas, 75601
Research Site
Memphis, Tennessee, 38120
Research Site
Midlothian, Virginia, 23114
Research Site
Milford, Massachusetts, 01757
Research Site
Nashville, Tennessee, 37203
Research Site
New Hyde Park, New York, 11042
Research Site
New York, New York, 10065
Research Site
New York, New York, 11355
Research Site
Norfolk, Virginia, 23502
Research Site
Omaha, Nebraska, 68130
Research Site
Oxford, Mississippi, 38655
Research Site
Park Ridge, Illinois, 60068
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Phoenix, Arizona, 85054
Research Site
Pittsburgh, Pennsylvania, 15213
Research Site
Portland, Oregon, 97213
Research Site
Ridgewood, New Jersey, 07450
Research Site
Rochester, Minnesota, 55905
Research Site
Salt Lake City, Utah, 84106
Research Site
San Antonio, Texas, 78240
Research Site
San Diego, California, 92123
Research Site
Santa Rosa, California, 92805
Research Site
Shirley, New York, 11967
Research Site
South Weymouth, Massachusetts, 02190
Research Site
St Louis, Missouri, 63110
Research Site
St. Petersburg, Florida, 33705
Research Site
Tacoma, Washington, 98405
Research Site
Waukesha, Wisconsin, 53226
Research Site
West Columbia, South Carolina, 29169
Research Site
York, Pennsylvania, 17403
Germany21 sites
Research Site
Ansbach, 91522
Research Site
Augsburg, 86156
Research Site
Bonn, 53111
Research Site
Chemnitz, 09116
Research Site
Dresden, 01307
Research Site
Erlangen, 91054
Research Site
Essen, 45130
Research Site
Freiburg im Breisgau, 79110
Research Site
Hösbach, 63768
Research Site
Immenstadt im Allgäu, 87509
Research Site
Koblenz, 56068
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Leipzig, 4103
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Mannheim, 68167
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München, 80634
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Paderborn, 33098
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Ratingen, 40878
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Ravensburg, 88212
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Regensburg, 93053
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Stade, 21680
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Tübingen, 72076
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Ulm, 89075
Japan21 sites
Research Site
Chiba, 260-8717
Research Site
Chūōku, 104-0045
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Hidaka-shi, 350-1298
Research Site
Hirakata-shi, 573-1191
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Kitaadachi-gun, 362-0806
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Kōtoku, 135-8550
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Kumamoto, 860-8556
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Matsuyama, 791-0280
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Nagoya, 464-8681
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Nagoya, 467-8602
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Niigata, 951-8566
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Osaka, 540-0006
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Osaka, 541-8567
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Ota-shi, 373-8550
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Sapporo, 003-0804
Research Site
Shinagawa-ku, 142-8666
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Shinjuku-ku, 162-8655
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Takasaki-shi, 370-0829
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Takatsuki-shi, 569-8686
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Tsukuba, 305-8577
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Yokohama, 241-8515
France19 sites
Research Site
Avignon, 84918
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Brest, 29200
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Clermont-Ferrand, 63050
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Dijon, 21079
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Limoges, 83000
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Lorient, 56322
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Lyon, 69373
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Marseille, 13273
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Metz-Tessy, 74370
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Nîmes, 30029
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Paris, 75248
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Rouen, 76021
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Saint-Cloud, 92210
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Saint-Herblain, 44805
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Toulouse, 31100
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Tours, 37000
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Vandœuvre-lès-Nancy, 54519
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Vantoux, 57070
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Villejuif, 94805
South Korea12 sites
Research Site
Cheonan-si, 31151
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Daegu, 42415
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Goyang-si, 10408
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Seongnam-si, 13620
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Seongnam-si, 463-712
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Seoul, 02841
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Seoul, 03080
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Seoul, 03722
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Seoul, 05505
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Seoul, 06273
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Seoul, 06351
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Seoul, 06591
United Kingdom12 sites
Research Site
Blackpool, FY3 8NR
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Cambridge, CB2 0QQ
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London, SW3 6JJ
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London, WC1N 3BG
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Manchester, M20 4BX
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Newport, NP10 8FZ
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Nottingham, NG5 1PB
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Portsmouth, PO6 3LY
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Reading, RG2 9LH
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Sheffield, S10 2SJ
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Sutton, SM2 5PT
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Taunton, TA1 5DA
Italy11 sites
Research Site
Bergamo, 24127
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Bologna, 40138
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Florence, 50134
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Meldola, 47014
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Milan, 20132
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Milan, 20141
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Misterbianco, 95045
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Naples, 80131
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Padova, 35128
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Roma, 00168
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Rozzano, 20089
Spain11 sites
Research Site
A Coruña, 15009
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Badalona, 08003
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Barcelona, 8035
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L'Hospitalet de Llobregat, 08908
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Madrid, 28040
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Madrid, 28041
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Málaga, 29010
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Murcia, 30008
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Sant Joan Despí, 08970
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Seville, 41013
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Valencia, 46010
Taiwan11 sites
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Kaohsiung City, 833
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Taichung, 40705
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Tainan, 70403
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Tainan, 710
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Taipei, 100
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Taipei, 110
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Taipei, 11259
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Taipei, 11490
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Taipei, 23561
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Taipei
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Taoyuan, 333
Portugal10 sites
Research Site
Guimarães, 4835-044
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Lisbon, 1400-038
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Lisbon, 1449-005
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Lisbon, 1500-650
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Lisbon, 1649-035
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Loures, 2674-514
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Porto, 4099-001
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Porto, 4200-072
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Porto, 4200-319
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Vila Nova de Gaia, 4434-502
Turkey (Türkiye)10 sites
Research Site
Adana, 01120
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Ankara, 06010
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Ankara, 06100
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Ankara, 06340
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Ankara, 06520
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Cordaleo, 35575
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Izmir, 35100
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Izmir, 35360
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Kadıkoy/Istanbul, 34722
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Kayseri, 38039
Bulgaria9 sites
Research Site
Haskovo, 6300
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Panagyurishte, 4500
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Pleven, 5804
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Plovdiv, 4004
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Sofia, 1303
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Sofia, 1330
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Sofia, 1407
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Sofia, 1431
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Sofia, 1527
Canada8 sites
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Calgary, Alberta, T2N 5G2
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Lévis, Quebec, G6V 3Z1
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Montreal, Quebec, H1T 2M4
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Montreal, Quebec, H2X 0C1
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Montreal, Quebec, H3T 1E2
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Ottawa, Ontario, K1H 8L6
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Québec, Quebec, G1S 4L8
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Vancouver, British Columbia, V5Z 4E6
Poland8 sites
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Bydgoszcz, 85-796
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Gdynia, 81-519
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Koszalin, 75-581
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Lodz, 90-302
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Poznan, 60-693
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Rzeszów, 35-001
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Tomaszów Mazowiecki, 97-200
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Warsaw, 02-781
Russia7 sites
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Moscow, 111123
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Moscow, 129090
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Moscow, 143423
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Nizhny Novgorod, 603126
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Podolsk, 142100
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Saint Petersburg, 194017
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Saint Petersburg, 197758
Hungary6 sites
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Budapest, 1062
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Budapest, 1122
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Miskolc, 3526
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Szekszárd, 7100
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Szolnok, 5000
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Zalaegerszeg, 8900
Israel5 sites
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Beersheba, 8410101
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Haifa, 3109601
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Jerusalem, 91120
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Petah Tikva, 494142
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Ramat Gan, 5262000
Slovakia5 sites
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Banská Bystrica, 974 01
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Bratislava, 833 01
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Košice, 041 91
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Michalovce, 07101
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Partizánske, 958 01
Austria4 sites
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Graz, 8036
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Innsbruck, 6020
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Salzburg, 5020
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Vienna, 1130
Belgium3 sites
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Leuven, 3000
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Liège, 4000
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Namur, 5000
Switzerland3 sites
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Bern, CH-3010
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Chur, CH-7000
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Winterthur, 8401
Australia2 sites
Research Site
Birtinya, 4575
Research Site
Darlinghurst, 2010
About this study
Official title: 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
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.
Read the detailed description
Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer.
This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well.
The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene.
Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:
- palbociclib + anastrozole
- palbociclib + letrozole
- abemaciclib + anastrozole
- abemaciclib + letrozole
- ribociclib + anastrozole
- ribociclib + letrozole
During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial.
In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative.
The researchers will look at which trial treatment helps the participants live longer with the cancer before it gets worse.
The researchers also want to know more about how safe AZD9833 is.
The trial participants will be split into 2 groups:
- Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo
- Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo
A placebo looks like a treatment but does not have any medicine in it.
A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.
The participants will take their trial treatments over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial.
Participants will visit their trial site regularly throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.
Participants will take their trial treatment until their cancer gets worse or they decide to leave the trial.
- Conditions
- ER-Positive HER2-Negative Breast Cancer
- Being tested
- AZD9833, AZD9833 Placebo, Anastrozole, Anastrozole placebo, Letrozole
- Keywords
- Metastatic, Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Physiological Effects of Drugs, Randomised, Multicentre, Double-Blind, Phase III, AZD9833, Next Generation Oral SERD, Anastrozole, Letrozole, Palbociclib, Abemaciclib, Ribociclib, Antagonists, Antineoplastic Agents, Estrogen Receptor Antagonists
- Medical subject headings
- Neoplasm Metastasis, Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9833Drug
Dosage formulation: AZD9833 tablets will be administered orally
AZD9833 PlaceboDrug
Dosage formulation: AZD9833 placebo tablets will be administrated orally.
AnastrozoleDrug
Dosage formulation: anastrozole tablets will be administered orally.
Anastrozole placeboDrug
Dosage formulation: anastrozole placebo tablets will be administrated orally.
LetrozoleDrug
Dosage formulation: letrozole tablets will be administered orally.
Letrozole placeboDrug
Dosage formulation: letrozole placebo tablets will be administered orally.
PalbociclibDrug
Dosage formulation: palbociclib tablets/capsules will be administered orally
AbemaciclibDrug
Dosage formulation: abemaciclib tablets will be administered orally
Luteinizing hormone-releasing hormone (LHRH) agonistDrug
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.
RibociclibDrug
Dosage formulation: ribociclib tablets will be administered orally
| Study group | Role | What they receive |
|---|---|---|
| AZD9833 + palbociclib, abemaciclib or ribociclib | Experimental | The 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) Receives: Drug: AZD9833; Drug: Anastrozole placebo; Drug: Letrozole placebo; Drug: Palbociclib; Drug: Abemaciclib; Drug: Luteinizing hormone-releasing hormone (LHRH) agonist; Drug: Ribociclib |
| Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib | Active comparator | The 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) Receives: Drug: AZD9833 Placebo; Drug: Anastrozole; Drug: Letrozole; Drug: Palbociclib; Drug: Abemaciclib; Drug: Luteinizing hormone-releasing hormone (LHRH) agonist; Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization until the earlier of the progression event or death (approximately 2 years)
Secondary outcomes (8)
Progression-free survival 2 (PFS2)
PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
Measured: 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)
The OS is defined as the time from randomization to death due to any cause.
Measured: From randomization until the date of death due to any cause (approximately 5 years)
Chemotherapy free survival
Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.
Measured: 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
ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1.
Measured: 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)
CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for At least 23 weeks after randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)
Measured: At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)
Change from baseline in EORTC QLQ-C30 scale scores
Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
Measured: From baseline until second progression (approximately 5 years)
Change from baseline in EORTC QLQ-BR23 scale scores
Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.
Measured: From baseline until second progression (approximately 5 years)
Plasma concentration of AZD9833 at specified timepoints
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.
Measured: on Day 15 for each patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2021
- Study start30 Jun 2021
- Primary completion30 Jun 2025
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ER-Positive HER2-Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 315 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04964934
- Sponsor's protocol ID
- D8534C00001
- Other IDs
- 2023-503990-39-00, 2021-000546-17, 2023
- Acronym
- SERENA-6
- Status last verified
- Sep 2026
- First submitted
- 30 Jun 2021
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Brufsky A, Park YH, Bidard FC, Mayer EL, Janni W, Ma C, Cristofanilli M, Bianchini G, Iwata H, Fasching PA, Nowecki Z, Pascual J, Chen SC, Moreau L, Ruiz-Borrego M, Shai A, Karadurmus N, Jung KH, Kikawa Y, Baird RD, Habash R, Sugarman R, Fox S, Selvi Miralles M, Huang Bartlett C, Turner N. SERENA-6 visual patient-reported outcomes and safety: camizestrant for emerging ESR1m advanced breast cancer during first-line endocrine-based therapy. Oncologist. 2026 Aug 6;31(9):oyag278. doi: 10.1093/oncolo/oyag278.
PubMed 42496653Turner NC, Mayer EL, Park YH, Janni W, Ma C, Cristofanilli M, Bianchini G, Kalinsky K, Iwata H, Chia S, Brufsky AM, Fasching PA, Nowecki Z, Pascual J, Karadurmus N, Gal-Yam E, Chung WP, Im SA, Zambelli A, Dalenc F, Oliveira M, Ishiguro H, Huang CS, Klinowska T, Fox S, Morrow C, Robert L, Huang-Bartlett C, Bidard FC. Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 2026 Aug;27(8):941-958. doi: 10.1016/S1470-2045(26)00287-1. Epub 2026 Jul 13.
PubMed 42442380Bidard 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.
PubMed 40454637Turner 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.
PubMed 37070653
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04964934
- Acronym / sponsor ID
- SERENA-6 / D8534C00001
- Conditions
- ER-Positive HER2-Negative Breast Cancer
- Keywords
- Metastatic, Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Physiological Effects of Drugs, Randomised, Multicentre
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 315 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 16 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer.
This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well.
The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene.
Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:
- palbociclib + anastrozole
- palbociclib + letrozole
- abemaciclib + anastrozole
- abemaciclib + letrozole
- ribociclib + anastrozole
- ribociclib + letrozole
During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial.
In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative.
The researchers will look at which trial treatment helps the participants live longer with the cancer before it gets worse.
The researchers also want to know more about how safe AZD9833 is.
The trial participants will be split into 2 groups:
- Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo
- Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo
A placebo looks like a treatment but does not have any medicine in it.
A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.
The participants will take their trial treatments over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial.
Participants will visit their trial site regularly throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.
Participants will take their trial treatment until their cancer gets worse or they decide to leave the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD9833 + palbociclib, abemaciclib or ribociclib | Experimental | Drug: AZD9833, Drug: Anastrozole placebo, Drug: Letrozole placebo, Drug: Palbociclib, Drug: Abemaciclib, Drug: Luteinizing hormone-releasing hormone (LHRH) agonist, Drug: RibociclibThe 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 comparator | Drug: AZD9833 Placebo, Drug: Anastrozole, Drug: Letrozole, Drug: Palbociclib, Drug: Abemaciclib, Drug: Luteinizing hormone-releasing hormone (LHRH) agonist, Drug: RibociclibThe 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) |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9833Dosage formulation: AZD9833 tablets will be administered orally | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib |
| AZD9833 PlaceboDosage formulation: AZD9833 placebo tablets will be administrated orally. | Drug | Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| AnastrozoleDosage formulation: anastrozole tablets will be administered orally. | Drug | Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| Anastrozole placeboDosage formulation: anastrozole placebo tablets will be administrated orally. | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib |
| LetrozoleDosage formulation: letrozole tablets will be administered orally. | Drug | Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| Letrozole placeboDosage formulation: letrozole placebo tablets will be administered orally. | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib |
| PalbociclibDosage formulation: palbociclib tablets/capsules will be administered orally | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib, Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| AbemaciclibDosage formulation: abemaciclib tablets will be administered orally | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib, Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| Luteinizing hormone-releasing hormone (LHRH) agonistMen (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist. | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib, Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
| RibociclibDosage formulation: ribociclib tablets will be administered orally | Drug | AZD9833 + palbociclib, abemaciclib or ribociclib, Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib |
Primary outcome
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1)
Time frame: From randomization until the earlier of the progression event or death (approximately 2 years)
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.
8 secondary outcomes
Progression-free survival 2 (PFS2)
Time frame: 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)
Time frame: From randomization until the date of death due to any cause (approximately 5 years)
Chemotherapy free survival
Time frame: 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
Time frame: 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)
Time frame: At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)
Change from baseline in EORTC QLQ-C30 scale scores
Time frame: From baseline until second progression (approximately 5 years)
Change from baseline in EORTC QLQ-BR23 scale scores
Time frame: From baseline until second progression (approximately 5 years)
Plasma concentration of AZD9833 at specified timepoints
Time frame: on Day 15 for each patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Derived from this study: PubMed 42496653Brufsky A, Park YH, Bidard FC, Mayer EL, Janni W, Ma C, Cristofanilli M, Bianchini G, Iwata H, Fasching PA, Nowecki Z, Pascual J, Chen SC, Moreau L, Ruiz-Borrego M, Shai A, Karadurmus N, Jung KH, Kikawa Y, Baird RD, Habash R, Sugarman R, Fox S, Selvi Miralles M, Huang Bartlett C, Turner N. SERENA-6 visual patient-reported outcomes and safety: camizestrant for emerging ESR1m advanced breast cancer during first-line endocrine-based therapy. Oncologist. 2026 Aug 6;31(9):oyag278. doi: 10.1093/oncolo/oyag278.
- Derived from this study: PubMed 42442380Turner NC, Mayer EL, Park YH, Janni W, Ma C, Cristofanilli M, Bianchini G, Kalinsky K, Iwata H, Chia S, Brufsky AM, Fasching PA, Nowecki Z, Pascual J, Karadurmus N, Gal-Yam E, Chung WP, Im SA, Zambelli A, Dalenc F, Oliveira M, Ishiguro H, Huang CS, Klinowska T, Fox S, Morrow C, Robert L, Huang-Bartlett C, Bidard FC. Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 2026 Aug;27(8):941-958. doi: 10.1016/S1470-2045(26)00287-1. Epub 2026 Jul 13.
- Derived from this study: PubMed 40454637Bidard 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.
- Derived from this study: PubMed 37070653Turner 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.
- Breast Cancer Study Locator details (for US)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
264 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZD9833, Anastrozole and Letrozole in people with ER-Positive HER2-Negative Breast Cancer, run by AstraZeneca at 264 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 264 sites in United States, Germany, Japan, France, South Korea and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1) (time frame: From randomization until the earlier of the progression event or death (approximately 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04964934, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.