Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and combined with abemaciclib, in recurrent/advanced ER-positive endometrioid endometrial cancer: Results from the phase 1a/1b EMBER study
- PMID: 39442371
- DOI: 10.1016/j.ygyno.2024.10.006
Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and combined with abemaciclib, in recurrent/advanced ER-positive endometrioid endometrial cancer: Results from the phase 1a/1b EMBER study
Abstract
Objective: Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor (ER) target inhibition. EMBER is a phase 1a/b trial of imlunestrant, as monotherapy and combined with targeted therapy, in patients with ER+ advanced breast cancer or endometrioid endometrial cancer (EEC). This report focuses on patients with ER+ EEC.
Methods: EMBER used an i3 + 3 dose-escalation design to determine the recommended phase 2 dose (RP2D) followed by dose-expansion cohorts (1:1 randomization): imlunestrant monotherapy and imlunestrant plus abemaciclib (150 mg twice daily). Eligible patients had measurable disease and progression or recurrence after platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor was not allowed. Secondary endpoints included safety, pharmacokinetics and antitumor activity.
Results: In total, 72 patients with a median of 2 prior anticancer therapies were treated. Among the 39 patients who received imlunestrant (400 mg [RP2D], n = 33; 800 mg, n = 6), the most common treatment-emergent adverse events (TEAEs) were grade 1-2 nausea (35.9 %), diarrhea (25.6 %), urinary tract infection (25.6 %), and abdominal pain (20.5 %). Overall response rate (ORR) was 10.3 %, clinical benefit rate (CBR) was 33.3 %, and median progression-free survival (mPFS) was 3.8 months (95 % CI, 1.8-6.7). Among the 33 patients who received imlunestrant (400 mg [RP2D], n = 29; 800 mg, n = 4) plus abemaciclib, the most common TEAEs were diarrhea (87.9 %), nausea (66.7 %), fatigue (48.5 %), and anemia (45.5 %). ORR was 18.2 %, CBR was 42.4 %, and mPFS was 6.8 months (95 % CI, 2.1-12).
Conclusion: Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.
Keywords: CDK4/6 inhibitors; SERD; Uterine cancer.
Copyright © 2024. Published by Elsevier Inc.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kan Yonemori: Institutional research support:MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly and company, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. Honoraria: Pfizer, Eisai, AstraZeneca, Eli Lilly and Company, Takeda, Chugai, Fuji Film Pharma, PDR pharma, MSD, Boeringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, Asteras, Bristol Myers Squibb, Novartis, Sanofi, Merk Biopharma. Advisory board: Eisai, Astra Zeneca, Sanofi, Genmab, Gliad, OncXerna, Takeda, Novartis, MSD, Henlius. Other: Principal investigator (to institution): MSD, Daiichi-Sankyo, Genmab, Seagen, AstraZeneca, Taiho, Merk Biopharma Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly and company, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. Valentina Boni: Institutional research support: Abbvie; ACEO; Adaptaimmune; Amcure; AMGEN; Amunix, AstraZeneca; Bycicle; BMS CytomX; GSK; Genentech/Roche; Genmab; Incyte; Ipsen; Janssen; Kura; Lilly; Loxo Therapeutics; Nektar; Macrogenics; Menarini; Merck; Merus; Nanobiotix; Novartis; Pfizer; PharmaMar; Principia; Puma; Ryvu; Ribbon; Sanofi; Taiho; Tesaro; BeiGene; Transgene; Takeda; Incyte; Innovio; MSD; PsiOxus; Seattle Genetics; Mersana; Daiichi; Nektar; Astellas; ORCA; Boston Therapeutics; Dynavax; DebioPharm; Boehringer Ingelheim; Regeneron; Rigontec; Millennium; Seagen; Synthon; Spectrum; Urogen; Zenith. Consulting fees: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart, Lilly; Janssen; EMD Serono; IDMC Nanobiotix NANORAY-312/Novartis; Steering Committee CytomX Therapeutics. Honoraria (speaking): Eli Lilly and Company; MSD; SOLTI; TACTICS; Getthi; Gedefo. Attending meeting and/or travel: Bayer (ESMO GI). Stock/Ownership: 1TRIALSP. Tarek M. Meniawy: Research funding: Bristol Myers Squibb, AstraZeneca, Merck Serono, Roche, BeiGene, MSD, Regeneron, Incyte, GSK. Advisory board: Novartis, GSK, MSD, Sanofi, Eisai, BMS. Attending meeting and/or travel: Bristol Myers Squibb. Peter A. Kaufman: Consulting fees: Eli Lilly and Company. Honoraria: Eli Lilly and Company. Attending meeting and/or travel: Eli Lilly and Company. Debra L. Richardson: Advisory board: Mersana, AstraZeneca, GSK, Immunogen, Eisai, ProfoundBio, Daiichi-Sankyo. Koji Matsumoto: Research funding: Daichi-Sankyo, MSD, Eli Lilly and Company, Gilead Sciences, Eisai. Honoraria: MSD, Kyowa Kirin, Daichi-Sankyo, Eli Lilly and Company, Chugai. Karthik V. Giridhar: Research funding: Guardant Health; Advisory board: AstraZeneca, Eli Lilly and Company, Novartis, Neogenomics, TerSera Therapeutics, Puma Biotechnology. Attending meeting and/or travel: Eli Lilly and Company, Grail Inc. José Angel García-Sáenz: Grants or contracts: Stemline Menarini, Jazz Pharmaceutical. Consulting fees: Stemline Menarini, Eli Lilly and Company. Advisory Board: Daiichi Sankyo, AstraZeneca, Eli Lilly and Company, Novartis, Gilead. Speaker's bureau: Eli Lilly and Company, Novartis, Astrofarma. Research funding: AstraZeneca. Attending meeting and/or travel: Roche, Novartis, Daiichi-Sankyo. Don S. Dizon: Consulting fees: GSK, Clovis and Pharma, Astra Zeneca, Kronos Biotech. Stock: Doximity, Midi Health. Els Van Nieuwenhuysen: Research funding: Eli Lilly and Company. Yujia Li; Shawn T. Estrem; Bastien Nguyen; Francesca Bacchion; Roohi Ismail-Khan are employees and stock owners of Eli Lilly and Company. Komal Jhaveri: Institutional research funding:Novartis, Genentech, Debiopharm group, ADC therapeutics, Pfizer, Novita Pharmaceuticals, Clovis oncology, Eli Lilly and Company, Zymeworks, Immunomedics, Puma Biotechnology, VelosBio/Merck, AstraZeneca, Context Therapeutics, Scorpion Therapeutics, Blueprint Medicines. Consulting fees: Novartis, Pfizer, AstraZeneca, Jounce Therapeutics, Synthon, Intellisphere, Bristol Myers Squibb, Genetench, Abbvie, Eli Lilly and Company, BluePrint Medicines, Seagen, Daiichi-Sankyo, Biotheranostics, Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead Sciences, Scorpion Therapeutics. Attending meeting and/or travel: Taiho Pharmaceutical, Jounce therapeutics, Pfizer, AstraZeneca, Intellisphere, Eli Lilly and Company, Gilead Sciences, Genetench/Roche. Kalyan Banda: Institutional research funding: Eli Lilly and Company, MorphoSys, Regeneron, Kineta, Pfizer; Honoraria: American Society for Clinical Oncology; Advisory Board: Astra Zeneca, Immunogen; Attending meeting and/or travel: American Society for Clinical Oncology. The other authors have completed conflict of interest forms and do not have potential conflicts of interest related to subject matter discussed in this manuscript to declare.
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