Giredestrant

2026年美国临床肿瘤学会（ASCO）年会于近日圆满落幕。罗氏在本届大会上公布了涵盖超过15个适应症的9款已上市及在研药物的最新研究数据，聚焦乳腺癌、血液肿瘤、肺癌及其他高负担癌种中未被满足的治疗需求。 “罗氏在ASCO展示的数据，体现了我们攻克高负担癌症、服务患者与社会的坚定决心。尤其是在乳腺癌领域，取得了多项重大进展，包括Giredestrant的最新研究结果以及HER2阳性转移性乳腺癌治疗方案上的持续演进。” Giredestrant是一款在研的新一代口服选择性雌激素受体降解剂（SERD）。三项III期临床试验数据发布，有望重塑未来早期及晚期HR+乳腺癌的治疗： ● lidERA研究（辅助治疗）：针对ER+/HER2-早期乳腺癌患者（已接受手术及按指征的辅助/新辅助化疗），无论其绝经状态如何，辅助治疗用Giredestrant均显示出较标准内分泌治疗更优的IDFS获益（绝经前患者HR为0.65，绝经后患者HR为0.74），接受Giredestrant治疗的患者因AE导致的治疗终止比例更低，且不论患者绝经状态如何，因骨骼肌肉疼痛导致的治疗终止比例也更低。 ● evERA研究（CDK4/6抑制剂耐药后）：在CDK4/6抑制剂耐药的ER+/HER2–晚期乳腺癌患者中，全口服联合方案Giredestrant联合依维莫司相比标准内分泌治疗联合依维莫司显著延长无进展生存期，且进一步延长第二次无进展生存期和无化疗生存期。对于研究所有患者及携带ESR1基因突变患者，该方案均能有效延迟后续治疗及后续化疗或ADC的使用，证明其临床获益在首次进展后仍具有持续性。 ● persevERA研究（一线内分泌敏感人群治疗）：比较Giredestrant联合哌柏西利与来曲唑联合哌柏西利作为内分泌敏感型ER+、HER2–局晚/转移性乳腺癌（LA/mBC）患者的一线治疗方案。在主要分析中，Giredestrant+哌柏西利相较于对照组显示出PFS数值上的改善（mPFS：33.1个月 vs 28.2个月；HR0.89；95%CI=0.76, 1.05；p=0.1553），但获益幅度未达到预先设定的统计学显著性阈值（HR0.85；p<0.0456），Giredestrant+哌柏西利耐受性良好。还待进一步探索Giredestrant一线获益人群，目前Giredestrant联合方案一线治疗内分泌耐药型ER+、HER2– LA/mBC患者的研究（pionERA研究）正在进行中。 同时，在罗氏引领了30多年的HER2+乳腺癌领域，创新药物同样迎来了全新突破： ● RG6596/ZN-A-1041（Ic期研究）：ZN-A-1041联合标准抗HER2治疗（T-DXd 或曲帕双靶），在伴有或不伴有脑转移的HER2+转移性乳腺癌患者中均展现出可控的安全性和突出的抗肿瘤活性, ZN-1041 600mg+T-Dxd治疗组ORR达到76.2% 。 ● SUNMO研究（III期）：（R/R LBCL）患者，莫妥珠单抗联合维泊妥珠单抗（Mosun-Pola）方案达到高的完全缓解率（CR率达60.7%），相较于传统免疫化疗（R-GemOx 方案）， Mosun-Pola组二线治疗R/R LBCL中位PFS提升近5倍（中位随访时间28.3个月，Mosun-Pola组mPFS达17.6个月，R-GemOx组3.6个月，HR=0.38），无论患者是否存在原发耐药或早期复发状态，整体安全性可控。该固定疗程、无化疗方案可能成为R/R LBCL患者新的选择 。 ● NP30179研究（I/II 期）：证实固定疗程的格菲妥单抗单药治疗重度经治包括BTKi治疗失败的高危复发难治套细胞淋巴瘤（ R/R MCL ）患者带来高且持久的完全缓解（总CR率达77%，中位随访时间41.5个月，中位DoCR达40.8个月），安全性整体可控。目前，一项全球多中心、III期临床试验（GLOBRYTE研究）评估格菲妥单抗单药治疗RR MCL患者的疗效及安全性正在进行中。 ● Krascendo 170研究(Ib/II 期）：证实新一代口服KRAS G12C抑制剂Divarasib联合帕博利珠单抗一线治疗晚期NSCLC展现出极具前景的疗效（ORR达72.9%，中位PFS达19.3个月）与可控的安全性。这一突破性数据成功为评估该联合方案一线治疗地位的全球III期 Krascendo 2研究提供了关键依据。 ● IMforte研究（III期）：基于Q-TWiST分析，通过TOX（出现≥3级治疗相关不良事件的时间）、TWiST（无严重症状且无严重毒性的时间）、REL（疾病进展至死亡时间）三个健康状态维度评估患者生活质量。结果证实接受芦比替尼联合Atezolizumab治疗组患者的平均TWiST时间为9.8个月，延长了生存获益，并确保了良好的生活质量。根据生物标志物分析结果，高TAM/高T-eff人群从联合治疗中获益突出，提示芦比替定可能通过微环境调节逆转免疫耐药。 ● IMvigor011研究（III期）：作为精准医疗的里程碑，研究证实通过ctDNA检测筛选出术后高危的肌层浸润性膀胱癌患者，接受Atezolizumab辅助治疗可显著降低36%的复发风险及41%的死亡风险，该方案已于2026年5月获美国FDA批准。 ● ATOMIC研究（III期）：作为全球首个证实免疫疗法在dMMR结肠癌辅助治疗中获益的III期研究，它表明术后半年FOLFOX化疗联合一年Atezolizumab的辅助方案可将III期患者的术后复发风险降低50%，开创了全新的临床标准治疗。此次ATOMIC研究的健康相关生命质量（HRQOL）数据重磅亮相，为Atezolizumab辅助治疗方案出色的耐受性提供了更有力的证据。 基于Giredestrant、Divarasib以及多款双特异性抗体、ADC药物的突破性前沿成果，罗氏计划在接下来的十年里，将为患者带来七款肿瘤及血液领域的颠覆性新药，助力应对全球每年新增逾1800万癌症病例的严峻挑战。 参考文献： [1]. Peter Schmid , et al. Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor–positive, HER2-negative early breast cancer (ER+, HER2- eBC) in the phase Ⅲ lidERA BC clinical trial: Results by menopausal status. 2026 ASCO Abs 502 [2]. Komal L. Jhaveri , et al. Post-progression treatment (tx) analyses of evERA Breast Cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in patients (pts) with estrogen receptor–positive, HER2-negative advanced BC (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor. 2026 ASCO 1016 [3]. Nicholas C. Turner, et al.Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): Primary analysis of the phase III persevERA BC trial. 2026 ASCO LBA1006 [4]. Kim w, et al. Mosunetuzumab plus polatuzumab vedotin (Mosun-Pola) versus rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL): Updated efficacy and safety from the Phase 3 SUNMO study including in second-line (2L) versus third-line plus (3L+) patient subgroups.  2026 ASCO. Abstract 7007. [5].  Karimi YH, et al. Fixed-duration glofitamab monotherapy in relapsed/refractory (R/R) mantle cell lymphoma (MCL) with/without prior Bruton's tyrosine kinase inhibitor (BTKi) exposure: Updated data after a 3.5-year follow-up. 2026 ASCO. Abstract 7006. [6]. Skoulidis F, et al. First-line (1L) divarasib plus pembrolizumab (pembro) in advanced or metastatic KRAS G12C+ non-small cell lung cancer (NSCLC): Results from the Krascendo-170 study. 2026 ASCO. Abstract 8510. [7]. Paz-Ares L, Borghaei H, Reck M, et al. IMforte: quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of first-line maintenance treatment with lurbinectedin + atezolizumab vs atezolizumab in extensive-stage small cell lung cancer. Poster presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. [8]. Paz-Ares LG, Borghaei H, Reck M, et al. Transcriptomic analyses of molecular subsets and correlations with clinical outcomes from the Phase 3 IMforte study of lurbinectedin + atezolizumab maintenance treatment in extensive-stage small-cell lung cancer. Rapid oral presentation at: 2026 American Society of Clinical Oncology Annual Meeting; May 31, 2026; Chicago, IL. [9]. Bellmunt J, et al. Patient-reported outcomes from IMvigor011: A phase 3 study of circulating tumor (ctDNA)–guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2026;44(15_suppl):abstract 462. Poster Bd: 106. [10]. Dueck AC, et al. Health-related quality of life (HRQOL) in the phase 3 trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair colorectal cancer (Alliance A021502, ATOMIC). J Clin Oncol. 2026;44(15_suppl):abstract 3626. Poster Bd: 393. 1.本新闻稿旨在分享研发前沿资讯，仅供中国境内医疗卫生专业人士参阅，非广告用途。 2.罗氏不推荐任何未被批准的药品、适应症的使用。 更多新闻 荣登顶刊《新英格兰医学杂志》！罗氏宣布ATOMIC研究达到主要终点，树立结肠癌辅助治疗新里程碑 罗氏佳罗华®治疗系统性红斑狼疮的III期ALLEGORY研究数据发表于《新英格兰医学杂志》，可显著降低疾病活动度

Roche (SIX: RO, ROP; OTCQX: RHHBY) has submitted a New Drug Application (NDA) to the US FDA for giredestrant, an investigational oral selective estrogen receptor degrader (SERD), as adjuvant treatment for adults with estrogen receptor (ER)-positive, HER2-negative stage I, II, and III breast cancer. The FDA has accepted the filing under Priority Review, marking a significant regulatory milestone for an oral SERD in the adjuvant breast cancer setting. The NDA, submitted under Priority Review, seeks approval for giredestrant as an adjuvant endocrine therapy in patients with ER-positive, HER2-negative early-stage breast cancer across stage I through III. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of 30 November 2026, the company said. Separately, Roche noted that the FDA has also accepted an NDA for giredestrant in combination with everolimus for ESR1-mutated ER-positive advanced breast cancer, with a decision expected in December 2026. The filing is supported by data from the lidERA Breast Cancer study (NCT04961996), a Phase III, randomized, open-label, multicenter trial evaluating adjuvant giredestrant versus standard-of-care endocrine therapy in patients with medium- or high-risk stage I–III ER-positive, HER2-negative breast cancer. The trial enrolled more than 4,100 patients, with invasive disease-free survival (iDFS) as the primary endpoint. Results demonstrated that giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with standard-of-care endocrine therapy (hazard ratio 0.70; 95% confidence interval 0.57–0.87; p\=0.0014). At three years, 92.4% of patients in the giredestrant arm were alive and free of invasive disease, compared with 89.6% in the standard-of-care arm. The iDFS benefit was reported as consistent across clinically relevant subgroups. Overall survival data were immature at the time of analysis, though a positive directional trend was observed. The treatment discontinuation rate was 5.3% with giredestrant versus 8.2% with standard-of-care endocrine therapy, suggesting a tolerability profile that may support adherence. Giredestrant is an oral, potent next-generation SERD and full estrogen receptor antagonist designed to block estrogen binding and trigger receptor degradation, thereby inhibiting tumor cell proliferation. The adjuvant ER-positive breast cancer treatment landscape has long been anchored by tamoxifen and aromatase inhibitors, with no new endocrine therapy class introduced in over two decades. The only approved oral SERD currently on the market is Menarini/Radius Health’s elacestrant (Orserdu), which holds an indication in the metastatic setting for ESR1-mutated disease rather than the early-stage curative context. Fulvestrant, an injectable SERD, is used in advanced disease but lacks an adjuvant indication. Giredestrant’s Phase III data in the adjuvant setting therefore positions it in largely uncontested regulatory territory among oral SERDs, though the broader selective estrogen receptor degrader breast cancer field continues to attract development activity. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.