Docetaxel

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) today announced detailed results from the Phase 3 HER2CLIMB-05 trial of the tyrosine kinase inhibitor TUKYSA® (tucatinib) as part of an investigational first-line maintenance treatment combination, following chemotherapy-based induction, in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). The primary endpoint analysis showed a 35.9% reduction in the risk of disease progression or death among patients treated with TUKYSA, trastuzumab, and pertuzumab compared to those treated with placebo, trastuzumab, and pertuzumab, as assessed by the investigator (hazard ratio [HR] of 0.641, 95% confidence interval (CI): 0.514-0.799; 2-sided p<0.0001). These findings were published today in the Journal of Clinical Oncology, shared in an oral presentation at the 48th San Antonio Breast Cancer Symposium (SABCS), and highlighted in the SABCS official press program. In HER2CLIMB-05, the median progression-free survival (PFS) was 24.9 months (95% CI: 21.3-not reached) in the TUKYSA arm and 16.3 months (95% CI:12.6-18.7) in the placebo arm, representing an extension in median PFS of 8.6 months. A PFS benefit was observed across all prespecified patient subgroups, including de novo or recurrent diagnosis, hormone receptor (HR)-positive or HR-negative disease, and with or without the presence or history of brain metastases at baseline. The key secondary endpoint of overall survival was not mature at the time of the analysis (20% of the required events have occurred to date) but showed a numerical trend for improvement with TUKYSA. “Most patients with HER2-positive metastatic breast cancer face disease progression within two years of starting first-line treatment, often requiring a transition to chemotherapy,” said Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director of Breast Cancer Research for Sarah Cannon Research Institute (SCRI). “These results demonstrate that adding tucatinib to first-line maintenance therapy extends the time patients live without their disease progressing, while maintaining a manageable safety profile, suggesting a promising new potential approach that could advance the current standard of care for HER2-positive disease.” TUKYSA in combination with trastuzumab and pertuzumab demonstrated a safety profile generally consistent with the established safety profiles of each individual therapy, except for a higher rate of asymptomatic Grade ≥3 liver transaminases, which were typically manageable and reversible with TUKYSA dose modifications and/or discontinuations. The most common adverse events observed in the TUKYSA combination arm were diarrhea, hepatic events, and nausea. “TUKYSA has become a trusted standard of care for patients with later-line HER2-positive metastatic breast cancer, and the results from HER2CLIMB-05 support its potential use as part of a chemotherapy-free, front-line maintenance strategy,” said Jeff Legos, Chief Oncology Officer, Pfizer. “At Pfizer, we are committed to advancing treatment options that meaningfully improve the lives of people with metastatic breast cancer, and we are proud to share these promising results for patients and their families.” TUKYSA is not currently approved for first-line treatment. The results from HER2CLIMB-05 will be discussed with regulatory authorities. Since its initial approval in 2020, TUKYSA in combination with trastuzumab and capecitabine has become a standard of care for HER2+ MBC patients in the third-line setting. TUKYSA is currently approved in more than 50 countries; in the United States, TUKYSA is approved for use in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. About HER2-Positive Metastatic Breast Cancer (MBC) HER2 is overexpressed in up to 15-20% of breast cancers and is associated with poor prognosis, with an estimated five-year survival rate for HER2+ MBC of 41-47%, depending on HR status.1-3 First-line standard-of-care maintenance treatment has remained unchanged since 2012, and the majority of patients with HER2+ MBC face disease progression within two years of initiating therapy.4 Until recently, there have been limited advancements for these patients. About the HER2CLIMB-05 Trial HER2CLIMB-05 is a randomized, double blind, placebo-controlled, pivotal Phase 3 study evaluating the efficacy and safety of TUKYSA® (tucatinib) compared to placebo, both in combination with trastuzumab and pertuzumab, as maintenance therapy for patients with HER2+ MBC following induction therapy in the first-line setting. Trial participants who completed induction therapy of trastuzumab, pertuzumab, and a taxane, with no evidence of progression were randomized to receive TUKYSA in combination with trastuzumab plus pertuzumab (n=326), or placebo in combination with trastuzumab plus pertuzumab (n=328). The primary endpoint is progression-free survival (PFS) as assessed by the investigator. Key secondary endpoints include overall survival. About TUKYSA® (tucatinib) TUKYSA (tucatinib) is an orally administered tyrosine kinase inhibitor of HER2. TUKYSA is approved in combination with trastuzumab and capecitabine to treat adults with HER2-positive advanced unresectable or metastatic breast cancer, including patients with brain metastases who have received one or more prior anti-HER2 breast cancer treatments in the metastatic setting. The full U.S. Prescribing Information for TUKYSA can be found here. IMPORTANT TUKYSA® (tucatinib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION Warning and Precautions: Diarrhea : TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB. Hepatotoxicity : TUKYSA can cause severe hepatotoxicity. Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase > 5 × ULN, 6% had an AST increase > 5 × ULN, and 1.5% had a bilirubin increase > 3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients. Embryo-fetal Toxicity : TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose. Adverse Reactions: In HER2CLIMB, serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥ 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock. Adverse reactions leading to treatment discontinuation occurred in 6% of patients who received TUKYSA. Adverse reactions leading to treatment discontinuation of TUKYSA in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions leading to dose reduction occurred in 21% of patients who received TUKYSA. Adverse reactions leading to dose reduction of TUKYSA in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%). The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. Laboratory Abnormalities: In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Disclosure Notice The information contained in this release is as of December 10, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology, TUKYSA® (tucatinib) and results from the Phase 3 HER2CLIMB-05 trial of TUKYSA as part of an investigational first-line maintenance combination therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC), including their potential benefits and plans to discuss the HER2CLIMB-05 results with regulatory authorities, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of TUKYSA; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the HER2CLIMB-05 trial will meet the secondary endpoint of overall survival; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when drug applications for TUKYSA may be filed in particular jurisdictions for any potential indications; whether and when regulatory authorities in any jurisdictions may approve any such applications that may be pending or filed for TUKYSA, which will depend on a myriad of factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether TUKYSA for any potential indication will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety, and/or other matters that could affect the availability or commercial potential of TUKYSA; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. References: Tarantino P, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. J An Onc . 2023;34(8):645-659. Wolff AC, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline focused update. J Clin Oncol . 2018;36(20):2105-2122. National Cancer Institute. https://seer.cancer.gov/statfacts/html/breast-subtypes.html . Accessed October 8, 2025. Swain SM et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol . 2020;21(4):519-530.

▲扫描小程序码报名观看 PREFACE 前言 自从康方生物凭借依沃西单抗（AK112）引爆整个PD-(L)1/VEGF双抗赛道后，PD-(L)1/VEGF双抗正在逐步取代PD-(L)1单抗，成为抗肿瘤新疗法的基石药。在核心玩家BioNTech、默沙东、辉瑞之后，新玩家荣昌生物近日也交出了新答卷。 2025 ESMO IO会议将于12月10日-12日在伦敦举行，荣昌生物公布了PD-1/VEGF双抗药物RC148，单药治疗或联合多西他赛治疗一线或二线局部晚期或转移性非小细胞肺癌（la/mNSCLC）无可操作基因组改变（AGA）的I/II期研究结果。 在PD-L1阳性一线转移性NSCLC患者中，RC148单药治疗的客观缓解率（ORR）为57.1%，疾病控制率（DCR）为100%；联合多西他赛治疗既往接受过PD-(L)1抑制剂和铂类化疗的患者中，ORR达66.7%，DCR达95.2%。 01 从后线治疗突围 区别于同类型的传统双抗，RC148在抗VEGF端采用了自主研发的创新纳米抗体，而非常用的贝伐珠单抗结构，分子量更小，组织穿透性可提升3-5倍，更易渗透实体瘤致密基质，直达肿瘤核心。 荣昌本次的研究旨在评估RC148单药治疗以及联合多西他赛治疗晚期/转移性NSCLC患者的疗效和安全性。具体来看，截至8月22日，第一阶段采用RC148单药治疗（20 mg/kg，每3周一次）22例一线PD-L1阳性的晚期/转移性NSCLC患者，ORR为57.1%，DCR为100%，6个月无进展生存期（PFS）率达89.7%。 更值得关注的是RC148在肺癌后线治疗领域的拓展。 第二阶段（队列1）纳入了42例既往接受过PD-(L)1抑制剂和含铂化疗（联合或序贯）治疗失败的驱动基因阴性局部晚期/转移性NSCLC患者，随机分组后，分别接受RC148（10 mg/kg）联合多西他赛或RC148（20 mg/kg）联合多西他赛治疗。 结果显示，20mg/kg剂量组联合多西他赛的ORR高达66.7%，DCR高达95.2%，中位PFS值达到8.3个月。安全性方面，单药治疗与联合治疗的整体耐受性良好，常见不良反应均为已知且可控的类型。 图源荣昌公开资料 经历了免疫（IO）治疗和化疗两大支柱疗法后疾病仍在进展的患者，治疗选择极少，患者预后极差，传统二线标准治疗（如多西他赛单药）的ORR约为15%，中位PFS约为4个月；同类双抗AK112+多西他赛治疗的ORR为40.0%，DCR为80.0%，中位PFS为6.6个月。 对比之下，RC148在肺癌2L+治疗领域的潜力已得到初步验证，凭借优异的临床数据，RC148已被CDE纳入同适应症的突破性疗法品种。今年8月，RC148也获FDA批准在美国开展针对多种晚期恶性实体瘤的II期临床试验，全球同步开发。 02 PD-(L)1/VEGF双抗的新答案 PD-(L)1/VEGF双抗的竞争已迈入深水区，面对康方、宜明昂科、辉瑞和默沙东等重磅玩家，荣昌对RC148的临床开发从一开始，就精准定位在“IO治疗失败后NSCLC”这一高未被满足需求的临床场景，构建差异化的竞争优势。 目前，康方也在推进AK112联合多西他赛治疗NSCLC后线患者的关键III期临床试验；BioNTech/普米斯/BMS的PM8002和三生/辉瑞的SG-707进度紧随其后，针对多个实体瘤适应症展开了II/III期临床。 开发策略和荣昌相似的是宜明昂科，其PD-(L)1/VEGF双抗IMM2510同样瞄准后线治疗肺癌患者，在一项针对经免疫治疗的晚期鳞状NSCLC的I期临床中，17例可评估疗效的患者中，整体ORR为29.4%，DCR为76.5%，中位PFS为9.4个月。 但荣昌在抗肿瘤领域的优势，不止双抗RC148，更有以维迪西妥单抗（RC48）为核心的多条ADC管线。 图源官网 荣昌已经围绕RC148展开了多项联用ADC治疗的临床研究，且联用进度领先。 在胃癌领域，RC118（CLDN18.2 ADC）+ RC148对比RC118 + PD-1单抗治疗CLDN18.2阳性、既往接受过≤2 线系统治疗的局部晚期或转移性胃/胃食管结合部腺癌患者的II期研究中，RC118+RC148治疗组ORR为52.4%（vs 33.3%），DCR为95.2%（vs 66.7%），6个月PFS率达75.0%（vs 33.4%）。 胃癌传统二线化疗ORR通常< 20%，PFS为3-4个月，RC118联用RC148有效实现了该领域的“疗效跃迁”。 在乳腺癌领域，RC148则在展开联合RC48（HER2 ADC）治疗既往接受过1-2线治疗失败的HER2低表达晚期乳腺癌患者的II期临床；再加上RC88（MSLN ADC）、RC278（靶点未披露）等ADC管线，未来荣昌在PD-(L)1/VEGF双抗+ADC联用治疗上还大有可为。 今年凭借泰它西普在干燥综合征上的突破，荣昌打了个漂亮的“翻身仗”。而在抗肿瘤新疗法的对抗中，要想从PD-(L)1/VEGF双抗的白热化竞争中突围，企业必须从临床未被满足的实际需求出发，并结合药物相互作用机制，开发切实有效的联合疗法。 相关研发工具 为了满足市场对PD-(L)1/VEGF双抗药物的开发需求，ACROBiosystems百普赛斯开发优化了一系列相关产品，包括高质量PD-(L)1及VEGF靶点蛋白；抑制剂筛选试剂盒；PD-(L)1过表达细胞株以及PD-1报告基因细胞株。这一系列产品可满足从免疫、抗体筛选和表征、细胞功能验证、信号通路研究到后期的生产质控全流程，协助加速多种疾病药物的研发。ACROBiosystems百普赛斯以“高质量、高适配性”的产品，持续缩短PD-(L)1/VEGF创新药研发周期，加速您的研发进程。 点击“阅读原文”查看详情。 扫码添加"小助手"，了解详情 注：资料转载自各大公司官网、公开信息源。版权归原作者所有，仅供读者学习、研究或者欣赏，不得用于商业用途，如涉及作品内容、版权和其他问题，请在30日内联系删除；本公众号对转载、分享的内容、陈述、观点判断保持中立，不对所包含内容的真实可靠性或完善性提供任何明示或暗示的保证，仅供读者学习、参考。本文仅为行业分析，不构成投资建议。股市有风险，投资需谨慎。 欢迎BD、研发小伙伴添加小助手进交流群 （请注明姓名+公司） ▲扫描小程序码报名观看 ▲点击图片链接查看详情 ▲点击图片链接查看详情 ↑点击图片长按识别二维码跳转相关链接