354TiP - A phase III randomised open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy (ET) in patients with ER+/HER2– early breast cancer (BC) and an intermediate or high risk of recurrence (CAMBRIA-1)

Background

Definitive locoregional (surgery ± radiotherapy) and standard adjuvant ET (± chemotherapy or cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) can achieve cure in many patients (pts) with ER+/HER2– early BC. Nevertheless, a significant proportion of pts with stage I–III disease will experience recurrence to metastatic, incurable disease (5- and 10-year cumulative incidences of recurrence of 8.3% and 14.0%, respectively). There is evidence that incorporating a more effective endocrine therapy after 2 years of standard adjuvant ET can result in clinical benefit for high-risk individuals. Camizestrant is a next-generation oral selective ER degrader and pure ER antagonist. In SERENA-2, camizestrant 75 mg and 150 mg significantly prolonged progression-free survival vs fulvestrant in postmenopausal women with ER+/HER2– advanced BC with disease recurrence or progression after ET. The CAMBRIA-1 study (NCT05774951) is evaluating the potential of extended adjuvant therapy with camizestrant to improve outcomes in pts with ER+/HER2– early BC with an intermediate or high risk of recurrence after definitive locoregional therapy and standard adjuvant ET.

Trial design

This phase 3 randomised, open-label study is enrolling women (pre- or postmenopausal) and men with ER+/HER2– (IHC 0/1+/2+/ISH–) early BC who have completed definitive locoregional therapy and standard adjuvant ET (± CDK4/6i) for ≥2 and ≤5 years (+ 3 months) without disease recurrence. Pts must be considered at intermediate or high risk of recurrence based on clinical, biological and genomic factors. Pts are randomised (1:1) to continue standard ET of the investigator’s choice (tamoxifen or aromatase inhibitor ± LHRH agonist) or camizestrant ± LHRH agonist for up to 60 months. The primary endpoint is invasive BC-free survival (STEEP 2.0 criteria). Secondary endpoints include invasive disease-free survival and distant relapse-free survival (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Approximately 4300 pts will be randomised; enrollment is ongoing.

Clinical trial identification

NCT05774951.

Editorial acknowledgement

Medical writing assistance was provided by Suzanne Patel at BOLDSCIENCE Inc., funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, Arcus, AstraZeneca, Daiichi Sankyo, SeaGen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan-Florentine, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, SeaGen, Abbvie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi-Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: SeaGen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, , Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Other, Other, EP14153692.0No financial interest, Institutional: Patent; Other, Other, EP21152186.9No financial interest, institutional: Patent; Other, Other, EP15702464.7No financial interest, institutional: Patent; Other, Other, EP19808852.8 No financial interest, Institutional: Patent. N. Niikura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Daiichi Sankyo, Chugai, Eli Lilly, MSD; Financial Interests, Personal and Institutional, Research Grant: Chugai, Eisai, Nippon Kayaku; Financial Interests, Personal and Institutional, Coordinating PI: Daiichi Sankyo. K.S. Saini: Financial Interests, Personal, Full or part-time Employment: Fortrea Inc.; Financial Interests, Personal, Stocks/Shares: Fortrea Inc., Labcorp Inc.; Financial Interests, Personal, Advisory Board: European Commission; Financial Interests, Personal, Ownership Interest: Quantum Health Analytics (UK) Ltd.; Non-Financial Interests, Personal, Other, Honorary Clinical Fellow: Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. I. Gioni: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. T. Klinowska: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Mayer: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Puma, Macrogenics, Sanofi; Financial Interests, Personal, Full or part-time Employment, since 12/2021: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech, Pfizer; Non-Financial Interests, , Member: ASCO, AACR. M. Stuart: Financial Interests, Personal and Institutional, Other, I provided consultancy support for AZ: AstraZeneca. E.I. Syta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Walding: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, SeaGen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.