Zenocutuzumab-zbco

LEXINGTON, Mass., Feb. 20, 2026 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced findings from a post hoc analysis of the eNRGy trial (NCT02912949) evaluating treatment beyond progression with zenocutuzumab in patients with advanced neuregulin 1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC). Results were presented at the 2026 International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer (TTLC) meeting. NRG1+ NSCLC is associated with low response rates and poor outcomes with non-targeted therapies, underscoring the need for effective targeted treatment options such as zenocutuzumab and potential use beyond progression. "Patients with advanced NRG1 fusion-positive non-small cell lung cancer often have limited treatment options after progression," said Dr. Misako Nagasaka, MD, PhD of the University of California Irvine and senior author. "In this analysis, continued zenocutuzumab treatment beyond RECIST progression provided meaningful, sometimes long-lasting, clinical benefit while maintaining a favorable tolerability profile." The analysis included 27 patients with NRG1+ NSCLC who received at least three doses of zenocutuzumab after radiographic progression. Oligoprogression occurred in 81% of patients, while 19% experienced diffuse progression. Median total zenocutuzumab exposure increased to nearly 10 months, compared with approximately 7 months before progression. Eight patients continued treatment for more than six months beyond progression, including one patient remaining on zenocutuzumab for more than 23 months after progression, with treatment still ongoing as of December 2025. Another patient remained on zenocutuzumab for nearly four years in total. Additionally, 22% of patients were able to continue zenocutuzumab following local management of progressing lesions including radiotherapy, gamma knife surgery, and surgical resection. Treatment was generally well tolerated, and no patients discontinued therapy due to adverse events. "These data underscore the potential heterogeneity of disease at progression and provide evidence that continued use of a targeted therapy, like zenocutuzumab, may offer meaningful clinical benefit without introducing new safety concerns," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "We continue to work with physicians to generate more information on the use of zenocutuzumab beyond progression." In December 2024, zenocutuzumab-zbco (BIZENGRI®) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). NRG1 gene fusions and other gene fusions are best detected using the combination of tissue-based DNA and RNA next-generation sequencing. For more information on the eNRGy trial and zenocutuzumab-zbco, please visit . About NRG1 Gene Fusions NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably the combination of tissue-based DNA and RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1. About BIZENGRI (zenocutuzumab-zbco) INDICATIONS BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information BOXED WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception. WARNINGS AND PRECUATIONS Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough. In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion. Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions. Interstitial Lung Disease/Pneumonitis BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed. Left Ventricular Dysfunction BIZENGRI can cause left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event. Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI. Embryo-Fetal Toxicity Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose. ADVERSE REACTIONS NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each). In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%). NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI. There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%). Please see full Prescribing Information, including Boxed Warning About Partner Therapeutics Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of therapeutics to improve health outcomes in cancer and serious diseases, as well as global health security threats. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. PTx's portfolio includes zenocutuzumab-zbco (BIZENGRI®) and sargramostim (EU: IMREPLYS®; US: LEUKINE®; and with Nobelpharma Co. Ltd for JAPAN: SARGMALIN®). Visit . References: 1. Arter ZL, Schram AM, Rha SY, et al. Continued treatment beyond progression with zenocutuzumab, a HER2/HER3 bispecific antibody, in patients with NRG1+ NSCLC: Analysis from the ongoing phase 2 eNRGy trial [abstract]. J Thorac Oncol. 2026. Poster presentation at International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer Meeting; Huntington Beach, CA; February 20, 2026. 2. Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic features and response to therapy of NRG1 fusion–driven lung cancers: The eNRGy1 global multicenter registry. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307 3. BIZENGRI (zenocutuzumab-zbco) injection [package insert]. Available at: 4. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion–positive cancer. N Engl J Med. 2025;392:566-76. doi: 10.1056/NEJMoa2405008 BIZENGRI® is a registered trademark owned by Merus B.V. Under an agreement with Merus, PTx has exclusive rights to develop, manufacture, and commercialize zenocutuzumab-zbco for the treatment of NRG1+ cancer in the U.S. and provide the product on a named-patient basis for this use outside of the U.S. pending future regulatory developments. PARTNER THERAPEUTICS®, IMREPLYS®, and LEUKINE® are registered trademarks owned by Partner Therapeutics, Inc. ©2026 Partner Therapeutics, All rights reserved. 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点击上方蓝字关注我们 ! 肺癌作为全球发病率和死亡率最高的恶性肿瘤，一直是医学研究的重点领域。近年来，随着靶向治疗和免疫治疗的快速发展，晚期非小细胞肺癌（NSCLC）患者的5年生存率已提升至24%~31%。然而，原发耐药、继发耐药和肿瘤异质性等问题仍未得到根本解决。广东省肺癌研究所的最新研究综述了肺癌新型治疗方法的机遇与挑战，为我们揭示了抗体偶联药物、双特异性抗体和细胞疗法等领域的突破性进展。 01 一、抗体偶联药物（ADC）：精准递送的"生物导弹" 抗体偶联药物（ADC）是一类由抗体、连接子和小分子细胞毒性药物组成的靶向生物制剂，兼具单克隆抗体的高选择性及化疗药物的细胞毒作用。其核心优势在于通过抗体的靶向作用，将细胞毒性药物精准递送至肿瘤组织，提高局部药物浓度并减少全身毒性。 1.1 热门靶点与代表药物 HER2靶点：德曲妥珠单抗（T-DXd）开创先河 德曲妥珠单抗（T-DXd，DS-8201）是NSCLC领域首个且目前唯一获批的抗HER2靶向药物。DESTINY-Lung02研究显示，在HER2突变NSCLC患者中，5.4 mg/kg和6.4 mg/kg剂量组的客观缓解率（ORR）分别为50%和56%，中位无进展生存期（PFS）分别为10.0个月和12.9个月。中国桥接研究DESTINY-Lung05进一步证实，在至少接受过一线治疗的中国患者中，确认的ORR达58.3%，疾病控制率（DCR）超过90%。 TROP2靶点：多药物竞争格局 TROP2（人滋养层细胞表面抗原2）通过调节钙离子信号通路和细胞周期蛋白表达促进肿瘤生长。目前主要药物包括： Dato-DXd（DS-1602）：在TROPION-Lung01和TROPION-Lung05的汇总分析中，ORR为43%，DCR达86.3%，尤其在EGFR-TKI耐药人群中显示出克服耐药的潜力 戈沙妥珠单抗（SG）：在TROPiCS-03研究中，治疗广泛期小细胞肺癌（ES-SCLC）的ORR为41.9%，但≥3级不良反应发生率高达74.4% 芦康沙妥珠单抗（SKB264/MK-2870）：国产原创TROP2-ADC，在经多线治疗的NSCLC患者中ORR达43.6%，中位总生存期（OS）长达22.6个月 HER3靶点：EGFR耐药新希望 HER3通过与EGFR形成二聚体参与EGFR靶向耐药。HERTHENA-Lung01研究显示，HER3-DXd在经EGFR-TKI和铂类化疗失败的患者中ORR为29.8%，中位PFS为5.5个月。值得注意的是，在基线有脑转移且未接受过放疗的患者中，颅内ORR达33.3%。 1.2 面临的挑战与未来方向 尽管ADC取得显著进展，仍面临诸多挑战：治疗相关不良事件、药物毒性、耐药性及肿瘤异质性。常见不良反应包括中性粒细胞减少症、血小板减少症等血液学毒性，以及间质性肺病（ILD）、周围神经病变等特殊毒性。 未来研究方向将聚焦于： 克服耐药：针对靶点下调、药物外排泵等机制开发新策略 优化安全性：降低肝毒性和肺特异性毒性 创新设计：双特异性ADC和双载荷ADC，如EGFR×HER3双抗ADC BL-B01D1在EGFR突变NSCLC中ORR达52.5% 02 二、双特异性抗体：精准靶向的"双重火力" 双特异性抗体（BsAb）能够与两个不同的抗原或同一抗原的不同表位特异性结合，具有桥接免疫细胞和肿瘤细胞、提高特异性、协同调控免疫应答等多重优势。目前已有多个双抗药物在肺癌领域获批或进入后期临床。 2.1 已获批的重要双抗药物 药物名称 靶点组合 适应证 关键临床数据 依沃西单抗（ivonescimab） PD-L1/VEGF EGFR-TKI进展后EGFR突变晚期非鳞状NSCLC二线治疗 中位PFS 7.1个月 vs 化疗4.8个月，ORR 50.6% vs 35.4% 埃万妥单抗（amivantamab） EGFR/c-MET EGFR外显子20插入突变NSCLC一线治疗 中位PFS 11.4个月 vs 化疗6.7个月，ORR 73% vs 47% tarlatamab DLL3/CD3 铂类耐药的广泛期SCLC ORR 40%，中位缓解持续时间9.7个月 zenocutuzumab HER2/HER3 NRG1融合阳性NSCLC ORR 33%，中位缓解持续时间7.4个月 2.2 双抗联合治疗的突破性进展 埃万妥单抗联合第三代EGFR-TKI lazertinib在MARIPOSA研究中，一线治疗EGFR经典突变晚期NSCLC的中位PFS达到23.7个月，显著优于奥希替尼单药的16.6个月（HR=0.7，P<0.001）。这一联合方案已获FDA批准，为EGFR突变患者提供了新的一线选择。 在奥希替尼耐药后治疗中，埃万妥单抗联合化疗的MARIPOSA-2研究显示，中位PFS延长至6.3个月（vs 化疗组4.2个月，HR=0.48，P<0.0001），ORR提高至53%（vs 29%），为奥希替尼耐药患者带来新希望。 2.3 面临的挑战与未来方向 双抗药物开发仍面临靶点选择、临床试验设计、副作用管理及疗效标志物确定等挑战。尤其在脑转移治疗方面，抗体类药物难以被动扩散穿过血脑屏障，限制了其在脑转移患者中的疗效。 未来研究将聚焦于： 发现更高特异性和更好安全性的新靶点 开发作用机制独特的靶点组合 通过结构优化和新型制剂提升血脑屏障穿透能力 建立准确预测疗效的生物标志物和PK/PD模型 03 三、基因和细胞疗法：唤醒免疫系统的"活药" 基因和细胞疗法代表了肺癌治疗的前沿方向，包括CAR-T细胞疗法、肿瘤疫苗、溶瘤病毒和NK细胞疗法等，为晚期肺癌患者提供了新的治疗选择。 3.1 CAR-T细胞疗法：精准识别的"定向导弹" 嵌合抗原受体T细胞（CAR-T）疗法通过基因工程技术改造患者自身T细胞，增强其对特定抗原的识别与杀伤能力。尽管在血液肿瘤中取得成功，但在实体瘤中仍面临抗原逃逸、肿瘤微环境抑制和毒性等挑战。 目前肺癌CAR-T临床试验主要靶向EGFR、CEA、MUC1等抗原： EGFR靶向CAR-T：在一项Ⅰ期临床试验中，11例肺癌患者接受治疗后，2例达到部分缓解（PR），5例疾病稳定（SD），且无明显毒副反应 CEA靶向CAR-T：约20余项临床试验正在开展，初步显示出一定的抗肿瘤活性 未来优化方向包括：多抗原识别设计、改善肿瘤微环境、优化CAR结构、开发"关闭开关"或"自杀基因"策略以限制毒性。 3.2 肺癌疫苗：激活自身免疫的"教育者" 肿瘤疫苗通过训练免疫系统识别癌细胞进行杀伤，主要包括基于细胞、病毒、肽和核酸的疫苗。其中，mRNA疫苗因其高效、安全且可快速定制化的特点，在肺癌治疗中展现出巨大潜力。 代表性疫苗进展： CIMAvax-EGF：古巴研发的EGF疫苗，Ⅲ期临床显示中位OS为12.4个月（vs 对照组9.4个月），5年生存率达23%（vs 0%） BNT116：BioNTech开发的mRNA疫苗，表达NSCLC常见肿瘤相关抗原，Ⅰ期LuCa-MERIT-1试验显示6例患者达到SD mRNA-4157（V940）：Moderna和默沙东联合开发，Ⅲ期INTerpath-009试验评估其与帕博利珠单抗联合用于可切除NSCLC的辅助治疗 3.3 其他细胞疗法：多元化的治疗策略 肿瘤浸润淋巴细胞治疗（TILs）：从肿瘤中提取并体外扩增的淋巴细胞，在黑色素瘤中已获批。在NSCLC的Ⅱ期研究中，对免疫治疗失败的患者ORR为21.4%，尤其在PD-L1阴性、低肿瘤突变负荷和STK11突变人群中显示活性。 溶瘤病毒疗法：通过改造病毒选择性裂解肿瘤细胞并激发免疫反应。STOMP研究显示，溶瘤病毒ADV/HSV-tk联合立体定向放疗和帕博利珠单抗治疗转移性NSCLC的ORR为33.3%，中位OS达18.1个月。 NK细胞疗法：先天免疫系统的重要组成部分，可直接识别并杀死癌细胞。研究显示，NK细胞联合PD-1抑制剂治疗NSCLC的中位OS达18.5个月，显著高于单用PD-1治疗的13.3个月。 04 四、展望：精准医学时代的肺癌治疗新策略 肺癌新型疗法正从靶向治疗向泛靶治疗、从后线治疗向一线治疗、从单药治疗向联合治疗转变。ADC和双特异性抗体已取得突破性进展，基因和细胞疗法也展现出有希望的前景。然而，免疫逃逸、药物毒性、肿瘤异质性等挑战仍需克服。 未来的研究方向将聚焦于识别关键肿瘤新抗原、克服T细胞耗竭、减少治疗毒性、提高T细胞效率，以及开发新一代靶向药物和联合治疗方案。通过基于生物标志物和基因组学的精准治疗，有望为肺癌患者提供更有效的治疗选择。 随着这些创新疗法的不断发展和优化，我们有理由相信，肺癌治疗将进入更加精准、高效和个体化的新时代，为患者带来更长的生存和更好的生活质量。 ●癌症治疗新革命！治疗性肿瘤疫苗全方位解析，这些突破值得关注 ●胆道癌 “不可切” 变 “可切”！三药联合转化治疗，63% 患者成功手术根治 ●结直肠癌免疫治疗新突破：mRNA+纳米抗体，精准激活抗癌免疫力！ ●哪怕11线治疗失败也有救？HER2阳性晚期实体瘤，后线治疗有新招 ●91%肿瘤显著缩小！这种“双锁”疗法，为HER2阳性乳腺癌按下“删除键” ●这一次，我们要赢！HER2 阳性胃癌患者，终于等来了这款“治愈系”新方案 ●绝境逢生！化疗无效、靶向耐药后，这款国产方案让晚期肠癌生存期翻倍 ●罕见癌不再“无药可救”！这种新方案让生存期突破33个月，九成患者病情受控 ●胃癌/食管癌患者的新希望：近半数实现“术后无癌”，这项《自然》研究值得细读！ ●柳叶刀重磅！肝内胆管癌术后防复发迎来“中国方案”，RFS超2年！ ●乳腺癌腋窝手术新共识：并非人人需要 “全清扫”，这类患者需谨慎！ ●KRAS G12C 突变结直肠癌有救了！格蕾西拉单抗联合治疗，50% 患者肿瘤缩小 ●胆道癌治疗新探索：HER2阳性患者的双药联合方案带来新希望