PO.CT01.04 · 临床试验

Elacestrant（Ela）联合everolimus（Eve）或abemaciclib（Abema）用于ER+/HER2-局部晚期或转移性乳腺癌（mBC）患者：ELEVATE（一项开放标签伞式研究）的2期结果

Elacestrant (Ela) in combination with everolimus (Eve) or abemaciclib (Abema) in patients with ER+/HER2- locally advanced or metastatic breast cancer mBC: phase 2 results from ELEVATE, an open-label, umbrella study

编号 CT262 展板 27 时间 4/21 02:00–05:00 区域 Section 50 主讲 Tomer Wasserman

分会场 Phase II Clinical Trials

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作者与单位 Authors & Affiliations

Hope S. Rugo¹, Sara M. Tolaney², Nancy Chan³, Giuliano Borges⁴, Rinat Yerushalmi⁵, Marina N. Sharifi⁶, Wassim McHayleh⁷, Thaddeus Beck⁸, Neelima Vidula⁹, Erika Hamilton¹⁰, Kristine J. Rinn¹¹, Joyce O’Shaughnessy¹², Giuseppe Curigliano¹³, Javier Cortés¹⁴, Paula Muñoz Romero¹⁵, Giulia Tonini¹⁵, Alessandro Paoli¹⁵, Monica Binaschi¹⁵, Li Cheng¹⁶, Jennifer A. Crozier¹⁶, Tomer Wasserman¹⁶, Virginia Kaklamani¹⁷

¹City of Hope Cancer Center, Duarte, CA,²Dana-Farber Cancer Institute, Boston, MA,³NYU Langone Health, New York, NY,⁴Catarina Pesquisa Clínica, Santa Catarina, Brazil,⁵Rabin Medical Center, Petah Tikva, Israel,⁶University of Wisconsin, Madison, WI,⁷Adventhealth Cancer Institute, Orlando, FL,⁸Highlands Oncology, Springdale, AR,⁹Massachusetts General Hospital, Harvard Medical School, Boston, MA,¹⁰Sarah Cannon Research Institute, Nashville, TN,¹¹Cancer Care Northwest, Spokane, WA,¹²Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX,¹³Istituto Europeo di Oncologia, IRCCS, and University of Milano, Milano, Italy,¹⁴International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Italy,¹⁵Menarini Group, Florence, Italy,¹⁶Menarini Group, New York, NY,¹⁷University of Texas Health Sciences Center San Antonio, San Antonio, TX

摘要 Abstract

中文摘要

背景：ER+/HER2- mBC患者在一线ET+CDK4/6i治疗中疾病进展与影响后续治疗疗效的耐药机制相关。在3期EMERALD试验中，Ela较标准治疗（SOC）ET改善了PFS（ESR1m肿瘤HR 0.55；95% CI 0.39-0.77；全部患者HR 0.70；95% CI 0.55-0.88），且安全性可控（Bidard 2022）。ELEVATE正在评估Ela与Eve、alpelisib、capivasertib、Abema、ribociclib或palbociclib的联合应用，以应对耐药机制。基于令人鼓舞的1b期结果，我们评估了Ela + Eve或Abema在全部患者及各亚组中的2期联合方案。方法：患有ER+/HER2- mBC、既往接受1-2线ET的患者符合入组条件，无论ESR1m状态如何。B臂（Ela + Eve）和C臂（Eve + Abema）要求既往接受过CDK4/6i。无既往CDK4/6i的患者入组D臂（Ela + Abema）。2期评估每种联合方案的PFS。在两种联合方案Ela + Eve（n=48）和Ela + Abema（n=50）的患者中评估了ESR1和PIK3CA突变状态。结果：截至2025年9月，50例患者入组B臂（Ela + Eve），60例入组C臂和D臂（Ela + Abema联合方案，各n=30）。基线特征为：伴内脏转移的患者（B臂72%，C/D臂92%）、原发性ET耐药（B臂20%，C/D臂15%）、ESR1m（B臂42%，C/D臂33%）及PIK3CAm（B臂50%，C/D臂27%）。各亚组间PFS一致（表1）。安全性结果与Eve或Abema + SOC ET的已知特征一致。2期Ela + Eve的ORR为19.5%，DCR为82.9%，mDOR为8.54个月。2期Ela + Abema的ORR为24.6%，DCR为91.2%，mDOR为14.75个月。结论：在ER+/HER2- mBC患者中，无论ESR1m状态如何，在ET±既往CDK4/6i治疗出现疾病进展后，Ela联合方案显示出一致且具有临床意义的PFS，并可能成为联合策略的ET骨架，支持全口服方案。表1：全部患者及各亚组的2期mPFS，月[95% CI]（*PFS未达到成熟[95% CI]）人群 Ela 345 mg QD + Eve 7.5mg QD（n=50） Ela 345 mg QD + Abema 150 mg BID（n=60） * 全部患者 8.3 [4.0 - 10.2] 14.3 [7.3 - 16.6] 内脏疾病 7.7 [3.7 - 9.4] 14.3 [7.4 - 16.6] 无既往fulvestrant 8.3 [4.2 - 12.9] 14.8 [8.7 - NR] 无原发性内分泌耐药 8.3 [4.0-12.9] 14.3 [7.3 - 16.6] ESR1m 8.3 [3.5 - 12.9] ESR1wt 9.0 [4.2 - 12.7] PIK3CAm 8.3 [3.6 - 10.2] PIK3CA wt 9.4 [4.0 - NR] NR，未达到 * 基因组亚组（ESR1/PIK3CA）或按既往CDK4/6i暴露分组的PFS（95% CI）未达到成熟。

查看英文原文 English abstract

Background: Disease progression in pts with ER+/HER2- mBC on 1L ET + CDK4/6i is associated with mechanisms of resistance that impact the efficacy of subsequent therapy. Ela improved PFS vs SOC ET ( ESR1 m tumors HR 0.55; 95% CI 0.39-0.77; all pts HR 0.70; 95% CI 0.55-0.88) with manageable safety in the Ph3 EMERALD trial (Bidard 2022). ELEVATE is evaluating Ela combined with Eve, alpelisib, capivasertib, Abema, ribociclib, or palbociclib to address resistance mechanisms. Based on encouraging Ph1b results, we evaluated Ph2 combinations of Ela + Eve or Abema in all pts and subgroups. Methods: Pts with ER+/HER2- mBC, 1-2L of prior ET are eligible regardless of ESR1 m status. Prior CDK4/6i is required for Arm B (Ela + Eve) and Arm C (Eve + Abema). Pts with no prior CDK4/6i were enrolled in Arm D (Ela + Abema). Ph2 evaluates PFS with each combination. ESR1 and PIK3CA mutation status were evaluated in pts for both combinations Ela + Eve (n=48) and Ela + Abema (n=50). Results: As of Sept 2025, 50 pts enrolled in Arm B (Ela + Eve), and 60 enrolled in Arms C and D (Ela + Abema combinations, n=30 each). Baseline characteristics are pts with visceral mets (72% Arm B, 92% Arms C/D), primary ET resistance (20% Arm B, 15% Arms C/D), ESR1 m (42% Arm B, 33% Arms C/D), and PIK3CA m (50% Arm B, 27% Arms C/D). PFS was consistent across subgroups (Table 1). Safety results were consistent with the known profiles of Eve or Abema + SOC ET. Ph2 Ela + Eve ORR was 19.5%, DCR 82.9%, mDOR 8.54 mo. Ph2 Ela + Abema ORR was 24.6%, DCR 91.2%, mDOR 14.75 mo. Conclusion: Ela combinations show a consistent clinically meaningful PFS irrespective of ESR1 m status in pts with ER+/HER2- mBC after progressive disease on ET ± prior CDK4/6i, and could become an ET backbone for combination strategies, supporting an all-oral approach. Table 1: Phase 2 mPFS, mo [95% CI] in all pts and subgroups (*Maturity not reached for PFS [95% CI]) Population Ela 345 mg QD + Eve 7.5mg QD (n=50) Ela 345 mg QD + Abema 150 mg BID (n=60) * All patients 8.3 [4.0 - 10.2] 14.3 [7.3 - 16.6] Visceral disease 7.7 [3.7 - 9.4] 14.3 [7.4 - 16.6] No prior fulvestrant 8.3 [4.2 - 12.9] 14.8 [8.7 - NR] No primary endocrine resistance 8.3 [4.0-12.9] 14.3 [7.3 - 16.6] ESR1m 8.3 [3.5 - 12.9] ESR1wt 9.0 [4.2 - 12.7] PIK3CAm 8.3 [3.6 - 10.2] PIK3CA wt 9.4 [4.0 - NR] NR, not reached * Maturity not reached for PFS (95% CI) for genomic subgroups ( ESR1 / PIK3CA ) or by prior CDK4/6i exposure.

利益披露 Disclosure

H. S. Rugo, Napo Pharmaceuticals, Bristol Meyer, Helsinn Therapeutics Consulting or Advisory Role. Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffmann-La Roche AG/Genentech, Inc, Stemline Therapeutics, Ambryx ). S. M. Tolaney, AADi; Ambrx; Artios Biopharmaceuticals; Arvinas; AstraZeneca; Bayer; BeiGene; Bicycle Therapeutics; BioNTech; Blueprint Medicines; Bristol-Myers Squibb; Circle Pharma; Cullinan Oncology; Daiichi Sank Other, Consulting or Advisory Role. eFFECTOR Therapeutics; Eisai; Genentech; Hengrui Pharmaceutical (USA); Immunomedics/Gilead; Incyte; Jazz Pharmaceuticals; Johnson & Johnson; Launch Therapeutics; Lilly; Menarini Group; Merck; Mersana Other, Consulting or Advisory Role. Natera; Novartis; Pfizer; Reveal Genomics; Sanofi; Seagen; Sumitovant Biopharma; Summit Therapeutics; Systimmune; Tango Therapeutics; Zentalis; Zuellig Pharma; Zymeworks Other, Consulting or Advisory Role. AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Daiichi Sankyo; Eisai (Inst); Exelixis (Inst); Genentech/Roche (Inst); Gilead Sciences (Inst); Jazz Pharmaceuticals (Inst) ). Lilly (Inst); Menarini/Stemlin (Inst); Merck (Inst); NanoString Technologies (Inst); Novartis (Inst); OncoPep (Inst); Pfizer (Inst); Seagen (Inst) ). Arvinas; Gilead Sciences; Jazz Pharmaceuticals; Lilly; Pfizer; Sanofi Travel. N. Chan, Daiichi Sankyo/Astra Zeneca; Novartis Other, Honoraria. Daiichi Sankyo Other, Consulting or advisory role. Merck ). G. Borges, None. R. Yerushalmi, AstraZeneca; Gilead Sciences; Lilly; Novartis; Pfizer; Rhenium Medical; Roche Other, Consulting or Advisory Role. Roche (Inst) ). M. N. Sharifi, Novartis (inst) ). W. McHayleh, AstraZeneca; Daiichi Sankyo/Astra Zeneca; Genentech; Gilead Sciences; Lilly; Natera Other, Consulting or Advisory Role. Agendia; AstraZeneca; Daiichi Sankyo/Astra Zeneca; Gilead Sciences; Lilly; Merck; Natera; Pfizer; Stemline Therapeutics Other, Speakers' Bureau. T. Beck, AbbVie (Inst); Amgen (Inst); AstraZeneca (Inst); DSi (Inst); Lilly (Inst); Nektar (Inst); Nektar (Inst); Novartis (Inst); Pfizer (Inst); Seattle Genetics/Astellas (Inst) ). N. Vidula, Daiichi; IDEOlogy Health; Novartis; Stemline Therapeutics Other, Consulting or Advisory Role. DAEHWA Pharmaceutical (Inst); Merck (Inst); Novartis (Inst); Pfizer (Inst); Radius Health (Inst); Stemline Therapeutics (Inst) ). E. Hamilton, Accutar Biotechnology (Inst); Arvinas (Inst); AstraZeneca (Inst); Circle Pharma (Inst); Daiichi Sankyo (Inst); Ellipses Pharma (Inst); Entos (Inst); Fosun Pharma (Inst); Genentech/Roche (Inst) Other, Consulting or Advisory Role. Gilead Sciences (Inst); Janssen (Inst); Jazz Pharmaceuticals (Inst); Jefferies (Inst); Johnson and Johnson (Inst); Lilly (Inst); Medical Pharma Services (Inst); Mersana (Inst); Novartis (Inst); Olema Other, Consulting or Advisory Role. fizer (Inst); Stemline Therapeutics (Inst); Tempus (Inst); Theratechnologies (Inst); Tubulis GmbH (Inst); Verascity Science (Inst); Zentalis (Inst) Other, Consulting or Advisory Role. Abbvie (Inst); Accutar Biotech (Inst); Acerta Pharma (Inst); ADC Therapeutics (Inst); Akeso Biopharma (Inst); Amgen (Inst); Aravive (Inst); ArQule (Inst); Artios (Inst); Arvinas (Inst); AstraZeneca ). AtlasMedx (Inst); BeiGene (Inst); Black Diamond Therapeutics (Inst); Bliss Biopharmaceutical (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squib (Inst); Cascadian Therapeutics (Inst); Clovis Onc ). 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(Inst); Tesaro (Inst); Tolmar (Inst); Torque (Inst); Treadwell Therapeutics (Inst); Verastem (Inst); Zenith Epigenetics (Inst); Zymeworks (Inst) ). K. J. Rinn, None. J. O’Shaughnessy, AADi; Agendia; Amgen; Aptitude Health; AstraZeneca; BioNTech; Bristol-Myers Squibb; Daiichi Sankyo; DAVA Oncology; DualityBio; Eisai; Ellipses Pharma; Exact Sciences; G1 Therapeutics; Genentech; Other, Honoraria. Gilead Sciences; Guardant Health; HiberCell; Jazz Pharmaceuticals; Johnson & Johnson; Lilly; Menarini Group; Merck; Mersana; Natera; Novartis Other, Honoraria. Pfizer; Pierre Fabre; Puma Biotechnology; Roche; Sanofi; Seagen; Stemline Therapeutics; Summit Therapeutics; Tempus; Tersera Other, Honoraria. AADi; Agendia; Amgen; Aptitude Health; AstraZeneca; BioNTech; Bristol-Myers Squibb; Daiichi Sankyo; DAVA Oncology; DualityBio; Eisai Other, Consulting or advisory role. Ellipses Pharma; Exact Sciences; G1 Therapeutics; Genentech; Gilead Sciences; Guardant Health; HiberCell; Jazz Pharmaceuticals; Johnson & Johnson; Lilly; Menarini Group; Merck; Mersana Other, Consulting or advisory role. Natera; Novartis; Pfizer; Pierre Fabre; Puma Biotechnology; Roche; Sanofi; Seagen; Stemline Therapeutics; Summit Therapeutics; Tempus; Tersera Other, Consulting or advisory role. Aptitude Health; Daiichi Sankyo; DAVA Oncology; Lilly; Merck; Novartis; Roche Travel. G. Curigliano, ESMO; ESMO Open; European Society of Breast Cancer Specialist Other, Leadership. Ellipses Pharma Other, Honoraria. AstraZeneca; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; Celcuity; Daichi-Sankyo; Exact Sciences; Foundation Medicine; Gilead Sciences; GlaxoSmithKline; Guardant Health; Hengrui Other, Consulting or advisory role. Lilly; Menarini; Merck; Novartis; Pfizer; Roche/Genentech; Samsung; Seagen; Veracyte Other, Consulting or advisory role. AstraZeneca; Daiichi Sankyo; Exact Sciences; Foundation Medicine; Gilead Sciences; Lilly; Menarini; Novartis; Pfizer; Roche/Genentech; Samsung; Seagen Other, Speaker's Bureau. Merck (Inst) ). AstraZeneca; Daichii Sankyo; Pfizer; Roche/Genentech Travel. J. Cortés, Leuko (I); MAJ3 Capital Stock. AstraZeneca; Celgene; Daiichi Sankyo; Eisai; Gilead Sciences; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Samsung; Steamline Therapeutics Other, Honoraria. Abbvie; AstraZeneca; Athenex; Bioasis; Biocon; Bioinvent; BioNTech SE; Boehringer Ingelheim; Bridgebio; Celgene; Cellestia Biotech; Circle Pharma; Clovis Oncology; Daiichi Sankyo; Delcath System Other, Consulting or Advisory Role. Ellipses Pharma; ERYTECH Pharma; Expres2ion Biotechnologies; GEMoaB; Gilead Sciences; GlaxoSmithKline; Hexagon Bio; HiberCell; Jazz Pharmaceuticals; Leuko; Lilly; Menarin Other, Consulting or Advisory Role. 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AstraZeneca; Daiichi Sankyo/UCB Japan; Lilly; Menarini; Puma Biotechnology; tersera Other, Consulting or advisory role. AstraZeneca/Daiichi Sankyo; Gilead Sciences; Novartis; Pfizer Other, Speaker's bureau. Eisai ).

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