Camizestrant in Combination with Three Globally Approved CDK4/6 Inhibitors in Women with ER+, HER2- Advanced Breast Cancer: Results from SERENA-1
Baird, R. D. Bermejo de Las Heras, B. Ruiz-Borrego, M. Vaklavas, C. Moreno, I. Oliveira, M. Armstrong, A. Turner, N. Incorvati, J. Twelves, C.
Baird, R. D.
Bermejo de Las Heras, B.
Ruiz-Borrego, M.
Vaklavas, C.
Moreno, I.
Oliveira, M.
Armstrong, A.
Turner, N.
Incorvati, J.
Twelves, C.
Abstract
PURPOSE: This trial investigated the safety and tolerability of camizestrant with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in women with estrogen receptor-positive, HER2- advanced breast cancer. PATIENTS AND METHODS: SERENA-1 (NCT03616587) is a phase I, multipart, open-label study in women with refractory estrogen receptor-positive, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg. Safety/tolerability, pharmacokinetics, efficacy, and impact on estrogen receptor 1 mutation ctDNA were assessed. RESULTS: By September 16, 2024 (data cutoff), 53 patients had received camizestrant plus abemaciclib, 78 camizestrant plus palbociclib, and 60 camizestrant plus ribociclib. Patients had a median of 2 (range, 0-7) prior regimens for advanced disease; 83% had received a prior CDK4/6i and 59% prior fulvestrant. The most common treatment-emergent adverse events for camizestrant 75 mg (phase III dose) plus each CDK4/6i were diarrhea [with abemaciclib (87.5%)] and neutropenia [with palbociclib (80%) and ribociclib (32.1% for 400 mg and 53.1% for 600 mg)]. The median camizestrant tmax was ∼4 hours postdose across combinations, with an estimated half-life of 9.5 to 17 hours. No clinically meaningful drug-drug interactions were evident. In this heavily pretreated population, CBR24 was 49.5% and the median progression-free survival was 7.4 months (95% confidence interval, 5.3-9.3), with antitumor activity across all combinations, including patients previously treated with CDK4/6i and/or fulvestrant, with or without estrogen receptor 1 mutation. CONCLUSIONS: Camizestrant is well tolerated, with antitumor activity in combination with CDK4/6i. These results support the evaluation of camizestrant 75 mg plus standard CDK4/6i doses in phase III trials.
Authors
Baird, R. D.
Bermejo de Las Heras, B.
Ruiz-Borrego, M.
Vaklavas, C.
Moreno, I.
Oliveira, M.
Armstrong, A.
Turner, N.
Incorvati, J.
Twelves, C.
Ciruelos, E.
Hamilton, E.
Patel, M. R.
Kabos, P.
Ciardullo, C.
Klinowska, T.
Lindemann, J. P. O.
Mathewson, A. M.
Morrow, C. J.
Sykes, A.
Yang, J.
Zhang, B.
Victoria, I.
Bermejo de Las Heras, B.
Ruiz-Borrego, M.
Vaklavas, C.
Moreno, I.
Oliveira, M.
Armstrong, A.
Turner, N.
Incorvati, J.
Twelves, C.
Ciruelos, E.
Hamilton, E.
Patel, M. R.
Kabos, P.
Ciardullo, C.
Klinowska, T.
Lindemann, J. P. O.
Mathewson, A. M.
Morrow, C. J.
Sykes, A.
Yang, J.
Zhang, B.
Victoria, I.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Baird RD, Bermejo de Las Heras B, Ruiz-Borrego M, Vaklavas C, Moreno I, Oliveira M, et al. Camizestrant in Combination with Three Globally Approved CDK4/6 Inhibitors in Women with ER+, HER2- Advanced Breast Cancer: Results from SERENA-1. Clinical cancer research : an official journal of the American Association for Cancer Research. 2025 Oct 15;31(20):4244-54. PubMed PMID: 40788187. Pubmed Central PMCID: PMC12521909 from AstraZeneca during the conduct of the study, as well as grants, personal fees, nonfinancial support, and other support from AstraZeneca outside the submitted work. B. Bermejo de las Heras reports personal fees from AstraZeneca, Gilead Sciences, Novartis, Pfizer, Eli Lilly and Company, and Menarini outside the submitted work. C. Vaklavas reports grants from AstraZeneca during the conduct of the study as well as grants from Pfizer, Seagen, H3 Biomedicine/Eisai, and CytomX; personal fees from Guidepoint, Novartis, Gilead Sciences, Pfizer/Seagen, Daiichi Sankyo, AstraZeneca, and Cardinal Health; and nonfinancial support from Genentech outside the submitted work. In addition, C. Vaklavas's spouse is employed by Flatiron. I. Moreno reports personal fees from Ellipses Pharma (advisory), Guidepoint (advisory group), and Getthi Group (speaker fee) outside the submitted work. M. Oliviera reports grants from AstraZeneca during the conduct of the study, as well as personal fees and nonfinancial support from AstraZeneca and Eisai; personal fees from Curio Science, Daiichi Sankyo, i-One, Eli Lilly and Company, Medscape, MSD, ProteinQure, and Relay Therapeutics; grants, personal fees, and nonfinancial support from Gilead Sciences and Hoffmann-La Roche; grants and personal fees from Pfizer; and grants from Immutep outside the submitted work. A. Armstrong reports other support from AstraZeneca during the conduct of the study, as well as grants from Gilead Sciences; personal fees from Gilead Sciences, Novartis, and Roche; and nonfinancial support from Roche and Novartis outside the submitted work. N. Turner reports advisory board honoraria from AstraZeneca, Eli Lilly and Company, Pfizer, Roche/Genentech, Novartis, GlaxoSmithKline, Repare Therapeutics, Inivata, Guardant Health, and Exact Sciences and research funding from AstraZeneca, Pfizer, Roche/Genentech, MSD, Guardant Health, Invitae, Inivata, Personalis, and Natera. C. Twelves reports nonfinancial support and other support from Novartis; personal fees, nonfinancial support, and other support from Pfizer; and personal fees and other support from Gilead Sciences, AstraZeneca, Eli Lilly and Company, and Daiichi Sankyo outside the submitted work. E. Ciruelos reports personal fees from AstraZeneca during the conduct of the study, as well as personal fees from Roche, Pfizer, Novartis, Daiichi Sankyo, Menarini Stemline, MSD, and Eli Lilly and Company outside the submitted work. E. Hamilton reports grants from AstraZeneca during the conduct of the study as well as grants from AbbVie, Artios, Atlas Medx, Bicycle Therapeutics, Biohaven Pharmaceuticals, BioNTech, Compugen, Cullinan, Dantari, Day One Biopharmaceuticals, Duality Biologics, Ellipses Pharma, Elucida Oncology, Exelixis, FujiFilm, Genmab, H3 Biomedicine, Iambic Therapeutics, ImmunoGen, Inspirna, InventisBio, Jacobio, Jazz Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, MabSpace Biosciences, Mabwell Bioscience, Marengo Therapeutics, Medilink Therapeutics, Merck, Novartis, Olema, Orinove, Orum Therapeutics, Pionyr Immunotherapeutics, Prelude Therapeutics, ProfoundBio, Regeneron, Relay Therapeutics, Rgenix, Seagen, Shattuck Labs, Simcha Therapeutics, Sutro, SystImmune, Taiho, Tesaro, TheRas, Treadwell Therapeutics, Verastem, Xadcera Biopharmaceutical, and Zymeworks; grants and other support from Accutar Biotech, Arvinas, AstraZeneca, BeiGene, Daiichi Sankyo, Gilead Sciences, Eli Lilly and Company, Mersana, Pfizer, Roche/Genentech, and Stemline Therapeutics; and other support from Circle Pharma, Entos, Halda Therapeutics, Incyclix Bio, IQVIA, Janssen, Jefferies LLC, Johnson and Johnson, Medical Pharma Services, Pyxis Oncology, Samsung Bioepis, Shorla Pharma, Tempus Labs, and Zentalis Pharmaceuticals outside the submitted work. M.R. Patel reports other support from AstraZeneca during the conduct of the study, as well as other support from ION Pharma, Daiichi Sankyo, UCB Japan, Kura Oncology, Accutar Biotech, Nurix, Mitsubishi Tanabe Pharma, Shivanka Research, Johnson & Johnson, Janssen, Agenus, Boehringer Ingelheim, Celgene, Cyteir Therapeutics, Genentech, Roche, Kymab, Loxo, Macrogenics, Merck, Moderna Therapeutics, Pfizer, Prelude Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Artios, Novartis, TeneoBio, Zymeworks, Olema, Adagene, Astellas, Compugen, Immunogen, Blueprint Pharmaceuticals, Cullinan Oncology, Immune-Onc Therapeutics, Immunitas, Ribon Therapeutics, Step Pharma, Bristol-Myers Squibb, Kineta, Hotspot Therapeutics, Conjupro Biotherapeutics, Allorion Therapeutics, Vividion Therapeutics, Georgiamune, AstraZeneca, Zai Lab, AbbVie, Avenzo, D3 Bio, OnCusp Therapeutics, Apollo, and Medlink outside the submitted work. P. Kabos reports grants from AstraZeneca, Cellcuity, Roche, OnKure, and Eli Lilly and Company outside the submitted work. C. Ciardullo reports other support from AstraZeneca outside the submitted work. T. Klinowska reports other support from AstraZeneca outside the submitted work. J.P.O. Lindemann reports other support from AstraZeneca outside the submitted work. A.M. Mathewson reports other support from AstraZeneca outside the submitted work. C.J. Morrow reports other support from AstraZeneca during the conduct of the study. A. Sykes reports other support from AstraZeneca during the conduct of the study, as well as other support from AstraZeneca outside the submitted work. J. Yang reports other support from AstraZeneca during the conduct of the study, as well as other support from AstraZeneca outside the submitted work. I. Victoria reports personal fees from MSD Oncology outside the submitted work. No disclosures were reported by the other authors. Epub 2025/08/11. eng.