Bevacizumab

2025年6月2日，美国旧金山和中国苏州——信达生物制药集团（香港联交所股票代码：01801），一家致力于研发、生产和销售肿瘤、心血管及代谢、自身免疫、眼科等重大疾病领域创新药物的生物制药公司，在2025年美国临床肿瘤学会年会（ASCO）上公布了全球首创（First-in-class）PD-1/IL-2α-bias双特异性抗体融合蛋白IBI363单药及联合贝伐珠单抗治疗晚期结直肠癌的临床研究数据。IBI363在传统定义为“免疫冷肿瘤”的结直肠癌中治疗观察到了显著响应和长期生存获益，印证了其独特的免疫激活机制，有望将“冷”肿瘤转变为“热”肿瘤。目前，信达生物正在中国、美国、澳大利亚同时开展临床研究，探索 IBI363 在免疫耐药、冷肿瘤和前线治疗等多瘤种适应症的有效性和安全性。本次ASCO会议，IBI363在首批探索的非小细胞肺癌、结直肠癌、黑色素瘤三项免疫耐药及冷肿瘤中，报道了令人鼓舞的I/II期临床数据，从肿瘤响应到长期生存获益，全面地展现了IBI363在各适应症的突破性临床研究结果。这是IBI363从创新药物机理到临床转化的扎实验证，并提示其进一步拓展临床开发的潜力，有望为免疫治疗空白的领域带来新希望。PD-1/IL-2α-bias双特异性抗体融合蛋白（IBI363）单药及联合贝伐珠单抗治疗晚期结直肠癌的I期临床研究数据本次研究数据来自两项I期临床研究（NCT05460767， NCT06717880），旨在评估IBI363单药及联合贝伐珠单抗治疗晚期结直肠癌受试者的安全性、耐受性和初步有效性。IBI363单药治疗即展现出突破性的抗肿瘤治疗潜力，总生存期较标准治疗数据显著延长截至2025年4月7日，共68例晚期结直肠癌受试者接受了不同剂量水平（0.1mg/kg-3mg/kg）的单药治疗。无已知的确认为高度微卫星不稳定（MSI-H），或错配修复蛋白缺陷（dMMR）受试者，86.8%的受试者为微卫星稳定（MSS）或错配修复蛋白完整（pMMR）的晚期结直肠癌。61.8%的受试者存在肝转移。63.2%的受试者既往接受过三线或以上的系统性抗肿瘤治疗。23.9%的受试者入组前接受过免疫治疗。接受IBI363单药治疗的患者中（n=68），中位随访时间为20.1个月，中位总生存期（OS）数据优异，达到16.1个月，相较标准治疗的过往研究数据（6.4-9.3个月1-3）有显著延长。亚组分析显示，无论是否有肝转移，患者均显示出优异的OS，提示显著临床获益。肝转移的受试者（n=42）中位OS为14.4个月，无肝转移的受试者(n=26)为17.0个月。 接受IBI363 单药1 mg/kg Q2W治疗患者中（n=22），总体确认的客观缓解率（cORR）为13.6%。IBI363联合贝伐珠单抗治疗展现出令人鼓舞的疗效信号及可控安全性，客观缓解率及无进展生存期数据优秀截至2025年4月7日，共73例晚期结直肠癌受试者接受了不同剂量水平（0.6mg/kg-3mg/kg）的IBI363联合贝伐珠单抗治疗。无已知确认为MSI-H或dMMR受试者, 91.8%的受试者为MSS或pMMR的晚期结直肠癌。56.2%的受试者存在肝转移。54.8%的受试者既往接受过三线或以上的系统性抗肿瘤治疗。16.4%的受试者入组前接受过免疫治疗。接受联合治疗的患者中（n=73），cORR为15.1%，疾病控制率（DCR）为61.6%。无进展生存期（PFS）中位随访时间为9.9个月， PFS达4.7个月。OS中位随访时间为9.4个月，OS未成熟，仅观察到13例事件（17.8%）。亚组分析显示，接受联合治疗无肝转移受试者中（n=32）, cORR为31.3%，DCR为81.3%。中位PFS达7.4个月。接受IBI363 3mg/kg Q3W联合治疗的受试者中（n=31），cORR和DCR分别提高至19.4%和71.0%，中位PFS达5.6个月。安全性方面，在接受单药和联合治疗受试者中，分别有19例（27.9%）和26例（35.6%）报告了3级及以上的治疗相关不良事件（TRAEs）。最常见TRAE是关节痛、贫血、皮疹和甲状腺功能减退。 IBI363单药治疗以及IBI363与贝伐珠单抗联合治疗均具有可接受的安全性特征，未观察到新的安全性信号。肿瘤免疫细胞浸润分析支持IBI363的将“冷肿瘤变热”的作用机制, 基线肿瘤组织中PD1⁺CD25⁺CD8⁺细胞的富集与临床疗效相关在基线肿瘤组织中的CD8⁺细胞、CD25⁺CD8⁺细胞和PD1⁺CD25⁺CD8⁺细胞的浸润水平升高与对IBI363单药治疗的临床反应改善（部分缓解或疾病稳定）相关。这在作用机制角度支持了IBI363在结直肠癌治疗中具有潜力的抗肿瘤效应。华中科技大学同济医学院协和医院张涛教授表示：“结直肠癌是严重危害人类健康的消化系统常见恶性肿瘤。在世界范围内结直肠癌发病率位居恶性肿瘤的第三位，死亡率位居恶性肿瘤的第四位4。约86%结直肠癌处于免疫荒漠或免疫炎症抑制状态，传统ICIs治疗无效5。对于标准治疗失败的结直肠癌，治疗手段有限，生存期短，存在巨大的未满足临床需求6。IBI363作为PD-1/IL-2α-bias双特异性分子，通过有效扩增肿瘤特异性CD8⁺ T细胞（TST细胞），在临床前研究中展现出强大的抗肿瘤效果。其阻断PD-1和刺激TST细胞的能力，有望将‘冷’肿瘤转变为‘热’肿瘤。IBI363单药在后线治疗的中位生存期可达16.1个月，对比于当前标准治疗方案的中位生存期有显著的提升，也证明其作为PD1+细胞因子双抗免疫疗法潜在强大的‘拖尾效应’。IBI363联合贝伐治疗组仍在持续随访，已显示出具有潜力的疗效及可耐受安全性，特别在无肝转移亚群中显示出独特的疗效特征。总体而言，已有的临床数据提示IBI363联合贝伐在结直肠癌人群具有充分的开发前景，值得进一步探索其临床价值。”信达生物制药集团高级副总裁周辉博士表示：“在2024年ASCO及ESMO报道的数据基础上，本次ASCO年会我们从ORR，PFS和OS及亚组分析等综合维度上更全面地展现了IBI363单药及联合疗法，在非MSI-H/dMMR晚期结直肠癌中展现了突破性的抗肿瘤活性，同时我们也期待高剂量组更长随访时间下的生存获益进一步成熟。IBI363针对晚期结直肠癌的关键研究计划正在准备中。同时，在传统定义为‘免疫冷肿瘤’的结直肠癌群体中观察到显著响应和长期生存获益，不仅印证了IBI363独特的免疫激活机制，更进一步提示了IBI363广谱开发潜力，有望为更多免疫治疗空白乃至更广泛的治疗领域带来希望。”关于IBI363（PD-1/IL-2α-bias双特异性抗体融合蛋白）- 滑动查看更多介绍 -IBI363是由信达生物自主研发的全球首创PD-1/IL-2α-bias双特异性融合蛋白，同时具有阻断PD-1/PD-L1通路和激活IL-2通路两项功能。IBI363的IL-2臂经过了设计改造，保留了其对IL-2 Rα的亲和力，但削弱了对IL-2Rβ和IL-2Rγ的结合能力，以此降低毒性；而PD-1结合臂可以同时实现对PD-1的阻断和IL-2的选择性递送。由于新激活的肿瘤特异性T细胞同时表达PD-1和IL-2α，这一差异性策略可以更精确和有效地实现对该T细胞亚群的靶向和激活。IBI363不仅在多种荷瘤药理学模型中展现出了良好抗肿瘤活性，在PD-1耐药和转移模型中也表现出了突出的抑瘤效力。从临床迫切需求出发，信达生物正在中国、美国、澳大利亚开展临床研究探索IBI363在针对各种恶性肿瘤的有效性和安全性。IBI363已开出首个关键注册临床研究，用于治疗未经免疫治疗的粘膜型和肢端型黑色素瘤。IBI363已获美国FDA两项快速通道资格认定，分别用于治疗晚期鳞状非小细胞肺癌和黑色素瘤。IBI363也获得中国NMPA纳入两项突破性疗法认证，治疗晚期黑色素瘤和鳞状非小细胞肺癌。关于信达生物- 滑动查看更多介绍 -“始于信，达于行”，开发出老百姓用得起的高质量生物药，是信达生物的使命和目标。信达生物成立于2011年，致力于研发、生产和销售肿瘤、自身免疫、代谢、眼科等重大疾病领域的创新药物，让我们的工作惠及更多的生命。公司已有15个产品获得批准上市，它们分别是信迪利单抗注射液（达伯舒®），贝伐珠单抗注射液（达攸同®），阿达木单抗注射液（苏立信®），利妥昔单抗注射液（达伯华®），佩米替尼片（达伯坦®），奥雷巴替尼片（耐立克®）， 雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®），伊基奥仑赛注射液（福可苏®），托莱西单抗注射液（信必乐®），氟泽雷塞片（达伯特®），匹妥布替尼片(捷帕力®)，己二酸他雷替尼胶囊（达伯乐®），利厄替尼片（奥壹新®）和替妥尤单抗N01注射液（信必敏®）。目前，同时还有3个品种在NMPA审评中，4个新药分子进入III期或关键性临床研究，另外还有15个新药品种已进入临床研究。公司已与礼来、罗氏、赛诺菲、Incyte和MD Anderson 癌症中心等国际合作方达成30多项战略合作。信达生物在不断自研创新药物、谋求自身发展的同时，秉承经济建设以人民为中心的发展思想。多年来，始终心怀科学善念，坚守“以患者为中心”，心系患者并关注患者家庭，积极履行社会责任。公司陆续发起、参与了多项药品公益援助项目，让越来越多的患者能够得益于生命科学的进步，买得到、用得起高质量的生物药。截至目前，信达生物患者援助项目已惠及20余万普通患者，药物捐赠总价值36亿元人民币。信达生物希望和大家一起努力，提高中国生物制药产业的发展水平，以满足百姓用药可及性和人民对生命健康美好愿望的追求。   详情请访问公司网站：www.innoventbio.com或公司领英账号：Innovent Biologics。声明：1.信达不推荐任何未获批的药品/适应症使用。2.雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®）和匹妥布替尼片（捷帕力®）由礼来公司研发。前瞻性声明本新闻稿所发布的信息中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用“预期”、“相信”、“预测”、“期望”、“打算”及其他类似词语进行表述时，凡与本公司有关的，均属于前瞻性表述。本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述是基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些是超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。本公司、本公司董事及雇员代理概不承担 (a) 更正或更新本网站所载前瞻性表述的任何义务;及 (b) 若因任何前瞻性表述不能实现或变成不正确而引致的任何责任。参考文献：1、 Dasari A, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023 Jul 1;402(10395):41-53. 2、 Grothey A, et al. CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. 3、 Mayer RJ, et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. N Engl J Med. 2015 May 14;372(20):1909-1919. doi: 10.1056/NEJMoa1414325.4、 https://publications.iarc.fr/Databases/Iarc-Cancerbases/GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalence-Worldwide-In-2012-V1.0-2012.5、 Huyghe N, et al. Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine. Cancers (Basel). 2022 Apr 29;14(9):2241. 6、 O'Neil BH, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PLoS One. 2017 Dec 28;12(12):e0189848.

SAN FRANCISCO, and SUZHOU, China, June 1, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, announces that the clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) monotherapy and combo-therapy with bevacizumab in advanced colorectal cancer were orally presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. IBI363 demonstrated encouraging response and overall survival benefit in the context of colorectal cancer, which is typically considered an immunologically 'cold' tumor, supports its unique mechanism of actions (MoA) of turning "cold tumor" into "hot tumor". Innovent Biologics is conducting clinical studies in China, the United States, and Australia to explore the efficacy and safety of IBI363 for multiple tumor indications, including immune resistance, cold tumors, and front-line treatments. At this year's ASCO meeting, IBI363 reported encouraging Phase 1/2 clinical data in the first three indications explored—non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and melanoma—focusing on IO-resistant and cold tumors. The data comprehensively demonstrated the breakthrough clinical outcomes of IBI363 across these indications, from robust tumor response to long-term survival benefits. These findings provide strong support of the drug's novel mechanism of action translating effectively into clinical outcomes, and imply its potential for broader clinical development, offering new hope in areas of immunotherapy where treatment options remain limited. PD-1/IL-2 α-bias bispecific antibody fusion protein IBI363 monotherapy and combined with bevacizumab in participants with advanced colorectal cancer: results from Phase 1 studies Two Phase 1 studies (NCT05460767, NCT06717880) were conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 monotherapy and combined with bevacizumab in patients with advanced colorectal cancer. IBI363 monotherapy has demonstrated breakthrough antitumor therapeutic potential, showing a significant extension of overall survival compared to data of standard-of-care therapies As of the data cutoff date (Apr 7th, 2025), a total of 68 participants with advanced colorectal cancer received IBI363 monotherapy at the dose levels from 0.1 mg/kg to 3mg/kg. No patients were confirmed as microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). 86.8% of patients were microsatellite stable (MSS) or proficient mismatch repair (pMMR). 61.8% of patients had liver metastases. 63.2% of patients had previously received 3 or more lines of systemic anti-tumor treatments. 23.9% of patients had received prior immunotherapy. Notably, among patients receiving monotherapy with IBI363 (n=68), with a median follow-up time of 20.1 months, the median overall survival (OS) reached 16.1 months, demonstrating a significant improvement compared to the historical data of standard treatments (ranging from 6.4 to 9.3 months1-3). Subgroup analyses revealed that patients with or without liver metastasis both showed excellent overall survival (OS), indicating significant clinical benefit. The median OS were 14.4 months (with liver metastasis) and 17.0 months (without liver metastasis). Among patients treated with monotherapy of IBI363 1 mg/kg every 2 weeks (Q2W) (n=22), the confirmed objective response rate (cORR) was 13.6%. The combination of IBI363 and bevacizumab demonstrated encouraging efficacy signals and a manageable safety profile, with excellent data on objective response rate and progression-free survival As of the data cutoff date (Apr 7th, 2025), a total of 73 patients with advanced colorectal cancer received IBI363 （dose levels from 0.6 mg/kg to 3mg/kg） and bevacizumab combination therapy. No patients were confirmed as MSI-H or dMMR. 91.8% of patients were MSS or pMMR. 56.2% of patients had liver metastases. 54.8% of patients had previously received 3 or more lines of systemic anti-tumor treatments. 16.4% of patients had received prior immunotherapy. In all participants treated with IBI363 in combination with bevacizumab (n=73), the cORR was 15.1% and the disease control rate (DCR) was 61.6%. With a median follow-up time of 9.9 months, the median progression free survival (PFS) reached 4.7 months. W ith a median follow-up time of 9.4 months, OS was not mature, with events in only 13 participants (17.8%). As for the combination therapy in patients without liver metastases (n=32), the confirmed ORR was 31.3%, with a DCR of 81.3%. The median PFS reached to 7.4 months. In those participants who received IBI363 at 3 mg/kg Q3W plus bevacizumab (n=31), confirmed ORR and DCR increased to 19.4% and 71.0%, respectively. The median PFS increased to 5.6 months. In terms of safety, among participants receiving monotherapy and combination therapy, 19 (27.9%) and 26 (35.6%) reported treatment-related adverse events (TRAEs) of Grade 3 or higher, respectively. The most common TRAEs were arthralgia, anemia, rash, and hypothyroidism. No new safety signals were observed, with a manageable risk-benefit profile in IBI363 alone or in combination with bevacizumab. Tumor immune cell infiltration analysis supports the IBI363 MOA of turning "cold tumor" into "hot tumor", demonstrating enrichment of PD1+CD25+CD8+ cells in baseline tumor tissue association with clinical efficacy In baseline tumor tissues, elevated infiltration of CD8+ cells, CD25+CD8+ cells, and PD1+CD25+CD8+ cells were associated with improved clinical response to IBI363 monotherapy (partial response or stable disease). This supports the potential anti-tumor effects of IBI363 in the treatment of colorectal cancer from the perspective of its mechanism of action. Professor Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated: "Colorectal cancer is the third most common cancer type globally and ranks fourth in cancer-related mortality4. About 86% of colorectal cancer are in an immune 'desert' or immune-inflamed suppressed state, rendering traditional immune checkpoint inhibitors (ICIs) ineffective5. For colorectal cancer that has failed standard treatments, there are limited therapeutic options with short survival periods, representing a significant unmet clinical need6. IBI363, as a PD-1/IL-2α-bias bispecific fusion protein, has demonstrated robust antitumor efficacy in preclinical studies through the effective expansion of tumor-specific CD8⁺ T cells (TST cells). Its ability to block PD-1 and stimulate TST cells holds the potential to transform 'cold' tumors into 'hot' tumors. As a monotherapy, IBI363 achieves a median survival of 16.1 months in later-line treatments, which represents a significant improvement compared to the median survival of current standard therapies and also confirms its potential with a strong 'tail effect' as a PD1 plus cytokine bispecific immunotherapy. The combination of IBI363 with bevacizumab is still under continuous follow-up, having shown promising efficacy and tolerable safety, with unique efficacy characteristics particularly in the subgroup without liver metastasis. Overall, clinical data suggest that IBI363 combined with bevacizumab holds significant promise for colorectal cancer and warrants further exploration." Dr. Hui Zhou, Senior Vice President of Innovent, stated: "On top of the preliminary data reported at 2024 ASCO and 2024 ESMO, we are presenting more updated follow-up data and combination therapy results of IBI363 at the ASCO Congress this year. From a comprehensive body of clinical evidence that includes ORR, PFS, OS, IBI363 demonstrated robust antitumor activity of both monotherapy and combination therapy in patients with advanced colorectal cancer who are non-MSI-H/dMMR. We are eyeing on long-term survival data from high dose in longer follow-up period. And the pivotal study of IBI363 targeting advanced CRC is in plan. Observing such results in the context of colorectal cancer, which is typically considered an immunologically 'cold' tumor, further highlights the broad development potential of IBI363. It offers hope for expanding into areas where immunotherapy has been less effective or even unresponsive." About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) IBI363 is a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein independently developed by Innovent Biologics. It functions by both blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 is designed to maintain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. This approach targets and activates tumor-specific T cells that express both PD-1 and IL-2α, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. In response to urgent clinical needs, Innovent is conducting clinical studies in China, the United States and Australia to further explore the efficacy and safety of IBI363 in various tumor indications, including immune-resistant, cold tumors, and front-line treatments. The first pivotal trial of IBI363 was initiated in 2025 for unresectable locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy. IBI363 has received two fast track designations (FTD) from the U.S. FDA and two breakthrough designations (BTD) from the China NMPA, for the treatment of squamous non-small cell lung cancer and melanoma, respectively. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: （1）Innovent does not recommend the use of any unapproved drug (s)/indication (s). （2）Ramucirumab (Cyramza®) and Selpercatinib (Retsevmo®) and Pirtobrutinib (Jaypirca®) were developed by Eli Lilly and Company. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. 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