Lenvatinib mesylate

IO 2.0 + ADC 2.0 Strategy Builds a "Next-Generation" Platform with Global Competitive Edge Key Highlights: Final analysis of HARMONi-A Study: Ivonescimab met the overall survival (OS) endpoint, demonstrating a statistically significant and clinically meaningful OS benefit First international Phase III HARMONi study of Ivonescimab: High concordance between international and Chinese data Ivonescimab secures approval for first-line treatment of NSCLC (significant positive outcomes from HARMONi-2 compared to pembrolizumab) sNDA for ivonescimab in first-line treatment of sq-NSCLC (significant positive findings from HARMONi-6 compared to tislelizumab + chemotherapy) Global development of ivonescimab: 13 registrational/Phase III trials (8 for lung cancer + 5 for major tumors including cold tumors and IO-resistant indications) Cadonilimab approved for first-line treatment of cervical cancer (inclusive of all patient populations), addressing global gap in immunotherapy for PD-L1 negative patients First international registrational clinical trial for cadonilimab: second-line HCC Global development of cadonilimab: 10 registrational/Phase III trials (including major tumors in first-line and IO-resistant indications) Inclusion of ivonescimab and cadonilimab in National Reimbursement Drug List (NRDL) IO2.0 + ADC2.0 strategy rapidly advancing, with global clinical development of next-generation ADCs such as AK146D1 bispecific ADC Penpulimab receives U.S. FDA approval, validating Akeso's international development and registration capabilities Immunology and autoimmune breakthrough: ebdarokimab (IL-12/IL-23) received market approval, with successful Phase III trials for gumokimab (IL-17) and from manfidokimab (IL-4Rα) HONG KONG, Aug. 26, 2025 /PRNewswire/ -- Akeso, Inc. (9926.HK) ("Akeso" or the "Company") announced its 2025 interim results for the six month period ending June 30, 2025, highlighting record commercial sales in China and major global advances in its oncology and autoimmune pipelines. The company has strengthened its leadership in IO bispecific antibodies for first-line cancers, cold tumors, and IO-resistant indications, while rapidly progressing next-generation bispecific-ADC therapies. Its "IO 2.0 + ADC 2.0" strategy is accelerating changes in the global oncology treatment landscape. Outside of oncology, Akeso is set to launch its third and fourth commercial products, boosting both its commercial portfolio and market capabilities. Driven by breakthrough clinical value, Akeso continues to optimize its oncology strategies, demonstrating leadership to reshape global treatment standards and clearly outlining its international expansion. Dr. Yu Xia, Founder, Chairwoman, President, and CEO of Akeso, said: "I want to sincerely thank the members of the Akeso family for their hard work, and also to say a big 'Thank You' to our partners for their strong support. Akeso has achieved historic results during this period. First of all, in the first half of this year, we reached record commercial performance. With expanded indications for ivonescimab and cadonilimab, coupled with accelerated market access following their inclusion in the National Reimbursement Drug List (NRDL), our innovation driven commercialization has gained significant momentum. Secondly, our 'IO 2.0 + ADC 2.0' strategy is establishing a lasting competitive advantage. Our first-in-class bispecific antibodies, cadonilimab and ivonescimab, position Akeso as a global leader in immuno-oncology bispecifics, reinforcing our pivotal role in shaping the future of cancer treatment. We are advancing the global development of both cadonilimab and ivonescimab in first-line cancers, cold tumors, and immuno-oncology resistant settings. Together, they are being evaluated in 23 registrational/Phase III trials and in over 20 Phase II studies worldwide, highlighting our strong commitment to research and development and providing a solid foundation for global growth. Notably, ivonescimab's initial Phase III trial demonstrated a statistically significant overall survival (OS) benefit, affirming its value across multiple endpoints, including progression-free survival (PFS) and OS. At the same time, our lead bispecific-ADC, AK146D1, and a next-generation ADC, AK138D1, have entered global early-stage clinical trials. Additional bispecific-ADC and ADC candidates are currently being developed. Both ivonescimab and cadonilimab are first-in-class drugs that have achieved regulatory approvals. Backed by their breakthrough clinical profiles and broad indication coverage, along with our leadership in global commercialization and a robust ADC pipeline that includes bispecific and next-generation platforms, we are now fully deploying our IO2.0 + ADC2.0 strategy worldwide. This positions us to build a transformative, long-term competitive advantage across our portfolio. Third, we are pioneering advancements in the field of autoimmune diseases and our non-oncology pipeline serves as a significant growth driver. With the recent launches of ebdarokimab (IL-12/IL-23) and ebronucimab (PCSK9), and upcoming launches of gumokimab (IL-17) and manfidokimab (IL-4Rα), alongside innovative candidates such as our IL-4R/ST2 bispecific and assets targeting neurological diseases, we are enhancing our non-oncology portfolio and broadening our competitive position globally. Backed by progress in R&D, clinical development, commercialization, and global strategy, Akeso has entered a new stage of growth. We remain committed to pioneering innovation, delivering transformative therapies to patients, and creating shared value for healthcare providers, patient communities, investors, and our team as we become a fully integrated global biopharma." Breakthrough IO Bispecific Antibodies Demonstrate Sustained Commercial Momentum with High-Quality Growth In the first half of 2025, Akeso's total commercial sales, net of distribution cost increased by 49.20% from RMB939.4 million for the six months ended June 30, 2024 to RMB1,401.6 million for the six months ended June 30, 2025. The growth underscores the company's robust commercial execution and deepening market penetration. Research and development expenses for the six months ended June 30, 2025 was RMB731.2 million. As of June 30, 2025, The company's total balance of cash, cash equivalents, time deposits, and financial products were RMB7,138.4 million. Key Growth Drivers Include: First-line Indication Approvals with Superior Clinical Profiles Cadonilimab in gastric and cervical cancers, and ivonescimab in NSCLC, are addressing critical unmet needs with clinically meaningful benefits, driving rapid adoption among physicians and patients. Enhanced Market Access via NRDL Inclusion Inclusion in China's National Reimbursement Drug List (NRDL) for cadonilimab (recurrent/metastatic cervical cancer) and ivonescimab (EGFR-TKI resistant NSCLC) significantly expands patient access and reduces out-of-pocket burden. Focused commercial efforts and clinician education accelerated uptake across key treatment centers. Diversified Growth from Non-Oncology Portfolio As the approvals for ebdarokimab (IL-12/IL-23) and ebronucimab (PCSK9) have followed one after another, the company's development efforts in non-oncology areas such as autoimmune diseases and metabolic diseases are beginning to significantly contribute to the growth of our commercial franchise. Ivonescimab Meets OS Endpoint in HARMONi-A Final OS Analysis; Demonstrates Potential to Reshape Global Treatment Landscape Across 8 Lung Cancer and 5 Other Major Tumor Indications Ivonescimab has consistently demonstrated superior efficacy compared to current IO 1.0 therapies, with an expanding number of global clinical program that includes multiple registrational and Phase III trials across a broad spectrum of tumors. With particular focus in first-line high-incidence cancers, cold tumors, and IO-resistant indications, ivonescimab further establishes its international leadership in cancer therapeutics. In August, Akeso announced that the final OS analysis of this clinical trial showed that ivonescimab met the OS clinical endpoint, demonstrating a statistically significant and clinically meaningful OS benefit. As the first Phase III final analysis for ivonescimab, these results not only reinforce its breakthrough value in progression-free survival (PFS), but also highlight its ability to deliver significant OS improvement, a key endpoint in global oncology drug development. During the reporting period, an interim analysis of the first global multicenter Phase III trial (HARMONi) also demonstrated strongly positive PFS outcomes. Although statistical significance for OS was not yet reached at the time of the announcement, a promising trend toward OS benefit was observed. With 38% of the patients enrolled from regions such as Europe and North America, the intent-to-treat (ITT) survival outcomes were highly consistent with those from the China-based HARMONi-A study, supporting ivonescimab's cross-regional consistency in efficacy and safety and enhancing its global market potential. Furthermore, following positive results from HARMONi-2—a randomized, double-blind, head-to-head Phase III trial against pembrolizumab monotherapy that led to its approval in first-line PD-L1-positive NSCLC (its second approved indication), ivonescimab plus chemotherapy has now also demonstrated significant positive outcomes in another head-to-head Phase III study against tislelizumab plus chemotherapy in first-line squamous NSCLC. This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared to PD-1 in combination with chemotherapy (the optimal standard of care for many cancer treatments), or compared to VEGF-related therapies in the area of anti-angiogenesis. This highlights the remarkable capability of ivonescimab to make leapfrog advancements in cancer treatment. Ivonescimab continues to validate its clinically meaningful profile and potential with a strategically expanded development program targeting key immuno-oncology settings: Phase III trials for Lung cancer (8 registrational/Phase III trials, 4 already met primary endpoints): First-line NSCLC, squamous and non-squamous (versus pembrolizumab + chemotherapy; global trial) First-line squamous NSCLC (versus tislelizumab + chemotherapy) NSCLC after progression on EGFR-TKI therapy (HARMONi-A and HARMONi studies) First-line PD-L1-positive NSCLC (versus pembrolizumab monotherapy) First-line PD-L1-high expressing NSCLC (versus pembrolizumab) IO-resistant NSCLC Consolidation therapy for limited-stage small cell lung cancer (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT) Phase III trials for core immuno-oncology indications (first-line therapy ): First-line biliary tract cancer (versus durvalumab + chemotherapy) First-line PD-L1-positive head and neck squamous cell carcinoma (HNSCC) in combination with ligufalimab (anti-CD47) versus pembrolizumab Phase III trials for cold tumors and more： First-line triple-negative breast cancer (TNBC) First-line MSS/pMMR colorectal cancer (representing about 95% of CRC cases) First-line pancreatic cancer Additional global Phase III trials are in advanced stages of planning An extensive clinical foundation includes over 20 Phase II studies across more than 10 additional tumor types, generating compelling efficacy and safety data to enable rapid transition to further registrational studies worldwide. Ivonescimab uniquely targets both PD-1 and VEGF, producing a synergistic anti-tumor effect. This dual mechanism not only combines the benefits of PD-1 and VEGF inhibition but also overcomes the efficacy and safety limitations of each target alone, resulting in pronounced clinical benefits. These advantages have been confirmed across multiple Phase III trials and real-world use, rapidly establishing ivonescimab as a next-generation leader in immunotherapy and anti-angiogenic therapy. For context, pembrolizumab (anti-PD-1) is approved for over 40 oncology indications, and bevacizumab (anti-VEGF) for more than 10. Akeso is implementing a dual-path strategy to maximize the value of ivonescimab world wide: accelerating domestic commercialization and label expansion in China, while simultaneously advancing global development in partnership with Summit Therapeutics. Cadonilimab Advances with Global Registrational Trial Launch Following Demonstration of Broad Efficacy Across 10 Major Tumor Types First-line Therapy and IO-Resistant Settings Cadonilimab is currently approved for recurrent/metastatic cervical cancer, first-line cervical cancer, and first-line gastric cancer, addressing significant unmet needs across multiple oncology indications. As the world's first approved immuno-oncology bispecific antibody, its breakthrough clinical value has been consistently demonstrated across numerous clinical studies and real-world applications. Robust evidence-based medical data confirms that cadonilimab delivers clinical benefit across a broad spectrum of patient populations, showing superior efficacy regardless of PD-L1 expression status. Furthermore, cadonilimab has exhibited significant clinical advantages over current standard therapies in multiple IO-resistant tumors and cold tumors that respond poorly to existing PD-1/L1 inhibitors. The benefits of cadonilimab stem from its unique ability to simultaneously target both PD-1 and CTLA-4, resulting in a synergistic anti-tumor effect. This innovative mechanism not only leverages the therapeutic advantages of both targets but also addresses the efficacy and safety limitations traditionally associated with them, culminating in significant clinical value. Notably, cadonilimab effectively overcomes the efficacy constraints often encountered with the toxicity of CTLA-4 monotherapies. These compelling advantages have been validated across multiple Phase III clinical trials and in real-world applications, positioning cadonilimab as a transformative advancement in the landscape of current immunotherapies. Cadonilimab is currently being evaluated in 10 global registrational/Phase III trials spanning first-line indications in major tumors, cold tumors, and IO-resistant diseases. Beyond its already approved indications (recurrent/metastatic cervical cancer, first-line cervical cancer, first-line gastric cancer), ongoing studies include: Combination therapy with pulocimab (anti-VEGFR-2) in PD-1-resistant gastric cancer (phase III) Perioperative treatment for resectable gastric cancer (phase III) First-line treatment of PD-L1-negative NSCLC (versus PD-1+ chemotherapy)(phase III) Consolidation therapy after concurrent/sequential chemoradiation in NSCLC (versus PD-L1 inhibitor) (phase III) Adjuvant therapy after hepatocellular carcinoma (HCC) resection (phase III) Intermediate-stage HCC (phase III) Global multicenter registrational Phase II trial is underway for the treatment of second-line HCC Notably, the first global multicenter registrational study of cadonilimab in combination with lenvatinib for the treatment of second-line HCC has recently been initiated (COMPASSION-36). This represents a significant milestone in its international development and regulatory pathway. The study aims to further validate cadonilimab's potential to overcome the limitations of single-target immunotherapies in global clinical practice, while also demonstrating the synergistic anti-tumor effect achieved through the dual targeting of PD-1 and CTLA-4. Additional multinational registrational and Phase III trials are currently in preparation. While advancing cadonilimab's global development independently, Akeso remains open to strategic collaborations to integrate worldwide resources and accelerate its international expansion, maximizing global patient reach and therapeutic value. Global Clinical Development of Bispecific ADCs, Leading a Transformative "IO 2.0 + ADC 2.0" Strategy in Oncology As IO-ADC combinations emerge as a pivotal direction in cancer therapy, Akeso as the only company globally with two approved immuno-oncology bispecific antibodies (cadonilimab and ivonescimab), is leveraging its strong leadership in the IO field to advance a next-generation pipeline of ADCs, bispecific ADCs, and dual-payload ADCs. Building on extensive international experience in bispecific/multispecific development, Akeso is combining its IO bispecifics with novel ADC platforms to create multidimensional, iterative treatment strategies aimed at redefining the global oncology landscape. The company has advanced its novel bispecific ADC targeting Trop2/Nectin4 (AK146D1) , and its differentiated novel HER-3 ADC (AK138D1) into global clinical development. Studies evaluating AK138D1 and AK146D1 in combination with cadonilimab or ivonescimab are currently in preparation. Additional next-generation internally developed ADCs, bispecific ADCs, and dual-payload ADCs are set to enter clinical trials in the future. Furthermore, ivonescimab and cadonilimab are also being widely explored in combination studies with ADCs from industry partners. Notably, Akeso's proprietary differentiated PD-1 inhibitor, penpulimab, has received approval from the U.S. FDA, making it the company's first internally developed innovative drug to be approved in the United States, and the first biologic entirely led (from R&D and clinical development to manufacturing and regulatory submission) by a Chinese company to achieve U.S. FDA approval. During the reporting period, other oncology assets also achieved key milestones: Akeso's in-house developed next-generation anti-CD47 antibody, ligufalimab, is being evaluated in multiple Phase III trials alongside cadonilimab and ivonescimab across several tumor types. Global clinical development of ligufalimab in hematologic malignancies is also ongoing The in-house developed pulocimab (VEGFR-2) is being evaluated in several Phase III trials in combination with cadonilimab and ivonescimab Two Additional Phase III Successes in Autoimmune Therapies Accelerate Non-Oncology Commercial Growth Beyond its oncology portfolio, Akeso has achieved significant milestones in autoimmune diseases with its in-house developed novel therapeutics: Ebronucimab (anti-PCSK9) has been approved in China for hypercholesterolemia, which affects approximately 110 million patients in China Ebdarokimab (anti-IL-12/IL-23) is approved in China for the treatment of psoriasis, a condition affecting around 6.7 million patients in China Gumokimab (anti-IL-17) has had its New Drug Application (NDA) accepted by NMPA for moderate-to-severe plaque psoriasis Additionally, gumokimab has achieved positive results in a Phase III trial for active ankylosing spondylitis, and manfidokimab (anti-IL-4Rα) has also reported Phase III success in atopic dermatitis. NDA submissions for these indications are currently underway The successive approvals and advanced development of these four non-oncology drugs enable Akeso to address diverse treatment needs across chronic, autoimmune diseases with large patient populations, creating a synergistic product portfolio that significantly enhances the company's competitiveness in the immunology sector. With further global innovations such as the IL-4R/ST2 bispecific antibody (AK139) and candidates targeting neurological diseases advancing through multi-indication development, Akeso continues to strengthen its non-oncology pipeline with first-in-class innovation. Moving forward, Akeso remains committed to pioneering novel therapeutics through original innovation. We will continue to develop medicines with global competitiveness, aiming to benefit patients worldwide and grow into a leading global biopharmaceutical company. About Akeso Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases. Among them, 24 candidates have entered clinical trials (including 15 bispecific/multispecific antibodies and bispecific ADCs. Additionally, 7 new drugs are commercially available. Through efficient and breakthrough R&D innovation, Akeso always integrates superior global resources, develops the first-in-class and best-in-class new drugs, provides affordable therapeutic antibodies for patients worldwide, and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise. For more information, please visit and follow us on Linkedin. SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

编者按 ESMO TAT ASIA 复发或转移性宫颈癌（r/mCC）患者预后较差，亟需新型治疗药物满足患者的治疗需求，尤其是PD-(L)1免疫治疗失败的患者仍缺乏“证据充分”的治疗选择。在近日举行的2025年ESMO TAT Asia大会上，国家癌症中心/中国医学科学院肿瘤医院安菊生教授代表研究团队汇报了II期EVER-132-003研究的更新数据，结果显示，靶向Trop-2的抗体偶联药物（ADC）戈沙妥珠单抗（SG）在经过多线治疗（包括免疫治疗）的r/mCC患者中显示出积极抗肿瘤活性和持久获益。《肿瘤瞭望》特邀在本次大会上进行口头报告安菊生教授，以及该研究PI、华中科技大学同济医学院附属协和医院李贵玲教授和该研究Leading PI、国家癌症中心/中国医学科学院肿瘤医院吴令英教授解读r/mCC诊疗现状及EVER-132-003研究意义。 安菊生 教授 国家癌症中心/中国医学科学院肿瘤医院 “更新的EVER-132-003研究显示，戈沙妥珠单抗用于多线经治的r/mCC具有积极的抗肿瘤活性和可控安全性，为Trop-2 ADC治疗r/mCC提供了重要的‘中国证据’，也为中国r/mCC患者带来了更多延续生存的治疗希望。” 李贵玲 教授 华中科技大学同济医学院附属协和医院 “Trop-2是新型ADC研发的热门靶点，在表达率较高的宫颈癌、卵巢癌、子宫内膜癌中，新型Trop-2 ADC戈沙妥珠单抗具有很好的应用前景。此次报道的EVER-132-003研究，为该新型药物在中国r/mCC患者中的应用提供了重要的循证医学证据，展现了巨大的应用价值。” 吴令英 教授 国家癌症中心/中国医学科学院肿瘤医院 “免疫治疗已经覆盖宫颈癌的局晚期、晚期一线和二线治疗，针对免疫经治患者亟需新型药物延续生存希望。EVER-132-003研究符合当前临床实践，戈沙妥珠单抗在免疫经治r/mCC患者中ORR 48%，DCR 96%，PFS 8.3个月，并显示出和整体人群一致的抗肿瘤活性和安全性。该新型Trop-2 ADC有望为中国宫颈癌患者提供新的治疗选择。” 01 研究介绍 安菊生 教授 国家癌症中心/中国医学科学院肿瘤医院 复发或转移性宫颈癌（r/mCC）在中国及全球的疾病负担依然沉重，此类患者预后极差，尤其是经过一线化疗和免疫治疗的患者，治疗选择十分有限。新型Trop-2抗体偶联药物（ADC）戈沙妥珠单抗（SG）已获批应用于晚期乳腺癌，在晚期子宫内膜癌也显示了积极的抗肿瘤活性。中国学者于2024年SGO大会口头报道的II期EVER-132-003研究显示，SG用于经治的r/mCC获得50%的客观缓解率（ORR），且安全性可控[1]。本次ESMO TAT Asia大会报道了该研究的更新数据[2]。 这是一项多中心、单臂、多队列、开放标签的II期临床试验，宫颈癌队列入组了40例对铂类及紫杉类耐药或不耐受的r/mCC患者（全体患者，FAS），其中27例（68%）既往接受过免疫治疗（Post-IO）。 基线特征 该研究入组患者大多为宫颈鳞癌（全体患者和免疫经治患者：85% vs 89%），也有少数腺癌（13% vs 7%）和腺鳞癌（3% vs 4%）。入组患者既往接受过较为复杂的多线治疗，全体患者和免疫经治患者分别有58%和75%的既往治疗线数为≥2线，分别有65%和70%的患者接受过靶向治疗，另外有部分患者接受过ADC或其他治疗。 图1. 患者人口统计学和疾病特征 疗效结局 SG在全体患者和免疫经治患者中ORR分别为43%（17/40）和48%（13/27）；疾病控制率（DCR）分别为85%（34/40）和96%（26/27）；中位治疗持续缓解（DOR）时间分别为9.2个月和9.5个月。 图2. 研究者评估的肿瘤缓解情况 生存结局 全体患者和免疫经治患者的中位PFS分别为7.1个月和8.3个月，1年PFS率分别为20%和27%；中位OS分别为16.5个月和17.2个月，2年OS率分别为38%和37%。 图3. 全体患者和免疫经治患者的PFS和OS 安全性 SG总体安全性可控、耐受性良好。全体患者≥3级治疗期间不良事件（TEAE）发生率为63%，较为常见的≥3级TEAE以中性粒细胞减少（43%）、白细胞减少（38%）、贫血（20%）等血液毒性为主，由治疗相关TEAE导致的停药率仅为5%（2例）。 图4. 安全性汇总 上述研究结果表明，单药SG用于经治的r/mCC患者，显示了持续的抗肿瘤活性和可控的安全性，且既往接受过免疫治疗的患者也有一致的临床获益。这些结果支持将SG用于治疗r/mCC，为中国患者提供潜在治疗选择。 02 研究者说 李贵玲 教授 华中科技大学同济医学院附属协和医院 近年来，ADC在众多晚期实体瘤领域取得突破性进展，为患者带来了新的治疗希望。其中，Trop-2是新型ADC研发的热门靶点；而SG是全球首个获批应用于晚期实体瘤临床实践的Trop-2ADC，从药物机制到临床研究均显示了多方面的巨大潜力。 首先，SG所靶向的Trop-2，是一种较少表达于正常组织而广泛表达于肿瘤细胞表面的跨膜蛋白，在宫颈癌（88.7%）、子宫内膜癌（96.2%）、卵巢癌（90.2%）中的Trop-2表达率均接近或超过90%[3-5]，目前，SG在不同实体瘤中的应用均无需依赖于Trop-2表达水平的检测，可覆盖全人群；再者，SG采用pH敏感的可水解连接子，与高活性的载药SN-38偶联而成，且药物抗体比（DAR）达7.6。一方面得益于药物精准递送和选择性裂解，能够降低循环脱靶效应、减少毒副作用，另一方面载药穿透细胞膜并发挥“旁观者效应”，作用于邻近肿瘤细胞，这些药物机制的优化使得SG具有高效、低毒的作用特征[6-7]。 EVER-132-003是一项多中心、单臂、多队列研究，我们中心也参与了该研究。去年SGO大会报道了宫颈癌队列18例患者的数据，SG显示了令人鼓舞的疗效和生存获益，ORR达50%，中位PFS也达到8.1个月；而此次ESMO TAT Asia大会更新的数据，样本量增加至40例，显示了持续一致的抗肿瘤活性和临床获益，ORR为43%，中位PFS为7.1个月，增加报道的生存数据还显示中位OS达16.5个月。安全性也与既往报道一致，SG较为常见的不良事件以血液毒性、胃肠道反应为主，此类事件临床易于管控，因此SG在经过多线治疗的r/mCC患者中也显示了良好的耐受性，停药率仅为5%。 目前，国内外已有多个不同靶点的ADC用于r/mCC治疗，大多为小样本I/II期临床试验。EVER-132-003研究入组患者经过多线治疗，而SG展现的抗肿瘤活性和生存数据令人鼓舞，从已报道的ADC相关研究来看表现出色[8-14]。因此，我们非常期待未来能够进一步开展扩大样本的随机对照研究加以验证，尽快为r/mCC患者提供新的治疗选择。 表1. 已报道ADC治疗r/mCC的临床研究（非头对头比较，请谨慎解读） 靶点 药物 研究 入组患者/治疗人群 主要研究结果 Trop-2 SG II期，EVER-132-003 58%接受过≥2线治疗，68%接受过免疫治疗 ORR 43%；DOR 9.2个月； PFS 7.1个月；OS 16.5个月 TF TV I/II期， innovaTV 201 51%接受过≥2线治疗，67%接受过贝伐珠单抗+双化疗；全人群 ORR 24%；DOR 4.2个月； PFS 4.2个月 TV II期, innovaTV 204 均为既往接受过≤2线化疗（其中2线30%）；全人群 ORR 24%；DOR 8.3个月； PFS 4.2个月；OS 12.1个月 TV联合 II期， innovaTV 205 D组，TV+卡铂一线治疗 ORR 54.5%；DOR 8.6个月； PFS 6.9个月，OS NR E组，TV+帕博单抗一线治疗 ORR 54.5%；DOR NR； PFS 5.3个月，OS NR F组，TV+帕博单抗二三线治疗 ORR 35.5%；DOR 14.1个月； PFS 5.6个月，OS 15.3个月 TV+pembro vs. 化疗  III期， innovaTV 301 既往接受过≤2线治疗（其中2线治疗38.4%），全人群 ORR：17.8% vs 5.4%； PFS：4.2 vs 2.9个月； OS：11.5 vs 9.5个月 HER2 T-DXd II期， DESTINY-PanTumor 一线治疗后复发的患者；HER2表达阳性 ORR 50.0%；PFS 7.0个月； OS 13.6个月 RC48 II期； RC48-C018 接受过≥1线治疗（2L、3L和4L+：48%、36%、16%)）；HER2表达阳性 ORR为36.4%；DOR 5.52个月；PFS 4.37个月 Nectin-4 9MW2821 I/II期， NCT05216965 接受过≤2线治疗（57.5%贝伐珠单抗＋含铂双化疗，60%免疫＋含铂双化疗）；全人群 ORR为40.54%；DCR 89.19%；PFS和OS均NR 03 Leading PI解读 吴令英 教授 国家癌症中心/中国医学科学院肿瘤医院 尽管宫颈癌是病因明确、具备完善三级预防体系，并被认为“有望彻底消除”的恶性肿瘤，但当前全球的宫颈癌发病率仍高居第4位[15]，是女性最常见的生殖系统恶性肿瘤之一，且死亡率居高不下，对全球及中国均造成沉重的疾病负担。宫颈癌的预后与肿瘤分期密切相关，早期疾病的5年生存率可达90%，而复发或转移性宫颈癌（r/mCC）的5年生存率则断崖式降低至17%[16]。近年来，各类新型药物的研发应用为r/mCC患者带来了新的治疗希望，其中针对不同靶点的新型ADC在宫颈癌、子宫内膜癌、卵巢癌等妇科肿瘤中也展现了积极的应用前景。 SG作为新型Trop-2 ADC，在全球包括我国在内的多个国家或地区已经被批准用于晚期乳腺癌治疗。我们牵头全国多中心开展的EVER-132-003研究中，SG用于经过多线治疗的r/mCC患者，显示了积极的治疗潜力。值得注意的是，该研究也报道了SG用于免疫经治患者的数据，ORR和PFS分别达到48%和8.3个月，表明SG在未经或经过免疫治疗的r/mCC患者均有一致的临床获益。 近年来，免疫治疗很大程度上改变了国内外宫颈癌治疗格局，在局晚期宫颈癌领域，基于KEYNOTE-A18研究，免疫联合同步放化疗的方案已经获批应用于FIGO 2014 III-IVA期宫颈癌治疗；在r/mCC领域，在含铂双药化疗±贝伐珠单抗基础上联合免疫治疗，为PD-L1阳性患者提供了新的一线治疗选择；而单药免疫治疗也成为MSI-H/dMMR患者二线及后线治疗的重要选择[17]。然而，对于免疫治疗失败患者的治疗策略，目前仍缺乏充分的循证医学证据。已有研究报道了免疫或免疫联合化疗、靶向治疗以及新型ADC等“再挑战”策略，ORR约为33%~53%，中位PFS约为6~7个月[18-20]。而在当前ADC单药治疗r/mCC的研究中，EVER-132-003是为数不多的明确提供了免疫经治患者治疗结局的研究，且显示了SG在免疫经治或未经治患者中有一致的临床获益。从这些单药治疗数据以及ADC联合免疫治疗具有协同增效的治疗潜力来看[1-2,21]，SG联合免疫治疗或可进一步提升疗效，并抬高r/mCC患者生存获益的“天花板”。 表2. 已报道免疫治疗进展r/mCC的临床研究（非头对头比较，请谨慎解读） 治疗方案 研究及入组患者 主要结果 卡度尼利单抗 （PD-1/CTLA-4双抗） 回顾性研究，17例抗PD-1进展的r/mCC患者 ORR 52.9%，单药、联合放疗、联合贝伐珠单抗的ORR分别为40%、50%和60% 卡度尼利单抗＋化疗 II期研究，24例免疫和化疗失败的r/mCC患者 ORR 52.4%，DCR 95.2%，PFS 6.2个月 赛帕利单抗＋仑伐替尼（抗PD-1＋TKI） II期研究，NCT05824468 ORR 33.3%，DCR 97.6%，PFS 7.1个月 TV（TF ADC）＋帕博利珠单抗 III期innovaTV 301，既往接受过≤2线治疗（其中27.5%接受过PD-1/PD-L1治疗） 免疫经治：HR 0.72 非免疫经治：HR 0.67 单药SG（Trop-2 ADC） II期EVER-132-003，68%接受过免疫治疗 ORR 48%，DCR 96%，PFS 8.3个月，OS 17.2个月 除了宫颈癌以外，SG在晚期子宫内膜癌（EC）也显示了积极的应用潜力，II期多队列TROPiCS-03研究显示，在既往接受过中位3线治疗的晚期EC患者中，SG治疗的ORR为22%，中位PFS为4.8个月，且安全性可控。目前，一项全球多中心的随机对照III期研究（ASCENT-GYN-01/GOG-3104/ENGOT-en26）正在开展，该研究将针对既往接受过含铂化疗和抗PD-(L)1免疫治疗的晚期EC患者，探讨SG对比医生选择化疗的疗效和安全性。期待未来有更多研究探索，为更多妇科肿瘤患者提供更加优效、安全的治疗选择。 参考文献 上下滑动查看更多内容 [1]An J, Li G, Zhang Y, et al. 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[18]Dapeng Li,et al.Real-world efficacy and safety of cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced, recurrent, and metastatic cervical cancer.SGO 2025 [19]Xiaoling Li,et al.A phase II study of cadonilimab plus chemotherapy in persistent recurrent/ metastatic cervical cancer patients who failed previous immuno/chemotherapy.SGO 2024 [20]Chunyan Lan,et al.Zimberelimab pluslenvatinib in patients withadvanced cervical cancer who progressed afterprior immune checkpoint inhibitors: a multicentersingle-arm,phase ll trial.SGO 2025 [21]Sara M. Tolaney, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 2025 ASCO LBA 109. 安菊生 教授 国家癌症中心 中国医学科学院肿瘤医院 副主任医师、硕士生导师 国家癌症中心国家肿瘤质控中心宫颈癌质控专家委员会委员 中国抗癌协会近距离放射治疗专业委员会常委 CSCO妇科肿瘤专家委员会委员 北京医学奖励基金会妇瘤专业委员会常委 全民健康素养促进分会青委会副主委 北京医学会妇科肿瘤学会青年委员 北京医师协会妇科分会青年委员 北京医学会放射肿瘤治疗学分会泛京津冀妇科肿瘤多中心专业协作组委员 中国精准放疗实用指南编委会专家 李贵玲 教授 华中科技大学同济医学院附属协和医院 医学博士、主任医师 武汉协和医院肿瘤中心副主任 武汉协和医院肿瘤中心肿瘤妇科主任 中国抗癌协会临床肿瘤学协作专业委员会副主任委员 中国医师协会近距离放疗专委会委员 湖北省抗癌协会理事 湖北省抗癌协会妇瘤专委会副主任委员 武汉市抗癌协会放疗专委会常务委员 第四届中国青年科技工作者协会委员 吴令英 教授 国家癌症中心/中国医学科学院 肿瘤医院辽宁医院 主任医师、博士生导师 北京协和医学院长聘教授 国家癌症中心/中国医学科学院肿瘤医院辽宁医院副院长 中国临床肿瘤学会(CSCO)副理事长 CSCO妇科肿瘤专家委员会主任委员 中国妇幼保健协会妇幼微创专业委员会主任委员 国家抗肿瘤药物临床应用监测委员会副主任委员 中国临床肿瘤学会临床研究专家委员会副主任委员 中国妇幼保健协会常务理事等 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。