Enfortumab Vedotin-ejfv

点击上方蓝字 关注我们 编者按：随着诊疗理念的发展与治疗手段的进步，肌层浸润性膀胱癌（MIBC）的治疗格局发生了重要变化。其中，抗体偶联药物（ADC）联合免疫检查点抑制剂的治疗方案，显著提高了病理完全缓解率，为患者保留膀胱提供了可能。然而，如何精准识别获益人群、有效控制膀胱内复发及转移风险，仍是当前亟待解决的关键问题。在近期举行的第15届上海泌尿肿瘤学术大会上，肿瘤瞭望-泌尿时讯特邀Vita-Salute San Raffaele大学泌尿生殖系统肿瘤中心主任Andrea Necchi教授就保膀胱策略的现状与未来进行深入剖析。 01 《肿瘤瞭望-泌尿时讯》 在您看来，基于新型药物（如ADC药物、免疫检查点抑制剂）的“联合强化治疗策略”，是否有潜力在未来改变高危患者的标准治疗方案，甚至取代一部分膀胱切除术？这其中面临的主要科学和临床挑战有哪些？ Andrea Necchi 教授 Vita-Salute San Raffaele大学 膀胱癌治疗领域正步入一个令人振奋的新阶段。随着免疫检查点抑制剂以及ADC药物（如维恩妥尤单抗）等新型疗法的相继问世，我们已在临床试验和临床实践中探索了联合应用。现有数据表明，ADC联合免疫检查点抑制剂作为新辅助治疗方案，能够带来较高的病理完全缓解率。这也引发了我们的思考：是否能够让达到深度缓解的患者免于接受根治性膀胱切除术？ 随着全身治疗效果的改善，越来越多的患者期望在治疗反应良好的情况下保留膀胱。然而，关键的挑战在于复发的不确定性。即便患者对全身治疗反应良好，选择保留膀胱后仍需面对膀胱内复发的风险，其中大多为高级别非肌层浸润性复发，这也是当前临床关注的焦点。因此，核心临床问题在于如何精准筛选适合保留膀胱的患者，并有效管控膀胱内复发，防止其发展为转移性疾病。去年于米兰召开的共识会议，正是为了明确“临床完全缓解”等概念，为患者筛选提供标准化的依据。 上下滑动查看英文对话 Oncology Frontier- UroStream: Professor, do intensive treatment strategies based on ADCs and ICIs have the potential to change the standard of care for high-risk bladder cancer patients and perhaps even replace radical cystectomy in the future? What are the primary scientific and clinical challenges involved? Dr. Necchi：The field of bladder cancer treatment is entering an exciting phase. With the successive emergence of ICIs and ADCs (such as enfortumab vedotin), we have begun exploring their combination in both clinical trials and practice. Existing data indicate that ADCs combined with ICIs as a neoadjuvant strategy can yield high pCR rates. This has led us to consider: can patients who achieve a deep response be spared from undergoing radical cystectomy? As systemic treatment outcomes improve, an increasing number of patients hope to retain their bladder when they respond well to therapy. However, the critical challenge lies in the uncertainty of recurrence patterns. Even if patients respond well to systemic therapy, those who choose bladder preservation still face the risk of intravesical recurrence, most of which are high-grade non-muscle invasive recurrences. Consequently, the core clinical issues are how to precisely screen suitable candidates for bladder preservation and how to effectively manage intravesical recurrence to prevent progression into metastatic disease. The consensus meeting held in Milan last year aimed specifically to clarify concepts such as "clinical complete response (cCR)" to provide a standardized basis for patient screening. 02 《肿瘤瞭望-泌尿时讯》 利用分子分型、液态活检（如ctDNA）或人工智能影像分析来预测肿瘤缓解情况，能否应用于指导保膀胱策略的制定和实施？您认为，未来我们是否能够建立一个可靠的生物标志物模型，为患者个体化选择保膀胱或根治性切除提供依据？ Andrea Necchi 教授 Vita-Salute San Raffaele大学 在疗效监测领域，我们已然迈入了新的阶段。一项重要的进展当属微小残留病灶（MRD）的评估，此概念在膀胱癌领域较新。当前常用的MRD评估方法包含两种“液体活检”方式：其一为基于患者肿瘤突变谱的个体化ctDNA分析；其二是基于相同原理的utDNA检测。 ctDNA是指由肿瘤细胞释放到血液中的小片段DNA，这些DNA片段携带着与原发肿瘤相关的遗传信息。通过检测ctDNA，可以实现对肿瘤的早期诊断、治疗效果监测以及复发风险评估等。目前，ctDNA已被确认为膀胱癌的预后生物标志物，且可对辅助免疫治疗（如膀胱切除术后应用阿替利珠单抗）的疗效进行预测。utDNA是指通过尿液样本检测到的肿瘤来源的DNA片段。它是一种非侵入性的生物标志物，与ctDNA类似，utDNA也携带肿瘤特异性突变信息，但其来源于尿液，因此在某些情况下可能更具优势。 然而，在围手术期新辅助或辅助治疗情镜下，特别是在指导保膀胱决策方面，ctDNA与utDNA的应用仍需更多可靠的数据予以支撑。从理论层面而言，倘若患者在新辅助治疗后ctDNA与utDNA均转为阴性，那么其可能是避免膀胱切除术、尝试保膀胱治疗的理想对象。但目前尚缺乏高级别的证据来明确这些生物标志物在保膀胱决策中的指导意义。不过可以确定的是，无论采用何种新辅助治疗方案，MRD评估正逐步改变着患者的治疗管理策略。 上下滑动查看英文对话 Oncology Frontier- UroStream: Can precision tools such as circulating tumor DNA (ctDNA), urinary tumor DNA (utDNA), or artificial intelligence (AI) imaging analysis provide guidance for bladder preservation? Is it possible to establish reliable biomarker models in the future to provide a basis for individualized patient choices between bladder preservation and radical cystectomy? Dr. Necchi：In the field of efficacy monitoring, we have entered a new stage. A significant advancement is the assessment of minimal residual disease (MRD), a concept that is still relatively novel in bladder cancer. Currently, common MRD assessment methods include two types of "liquid biopsy":Individualized ctDNA analysis based on the patient's tumor mutation profile and  utDNA detection based on the same principle. ctDNA refers to small fragments of DNA released into the blood by tumor cells, carrying genetic information related to the primary tumor. Detecting ctDNA enables early diagnosis, treatment monitoring, and recurrence risk assessment. Currently, ctDNA has been confirmed as a prognostic biomarker for bladder cancer and can predict the efficacy of adjuvant immunotherapy (such as atezolizumab after cystectomy). utDNA refers to tumor-derived DNA fragments detected in urine samples. As a non-invasive biomarker similar to ctDNA, utDNA also carries tumor-specific mutation information; however, because it originates from urine, it may offer advantages in certain contexts. Nevertheless, in the perioperative neoadjuvant or adjuvant setting—particularly regarding the guidance of bladder preservation decisions—the application of ctDNA and utDNA still requires more reliable data for support. Theoretically, if both ctDNA and utDNA turn negative following neoadjuvant therapy, the patient may be an ideal candidate for attempting bladder preservation. However, there is currently a lack of high-level evidence to define the guiding significance of these biomarkers in bladder preservation decision-making. What is certain is that, regardless of the neoadjuvant regimen used, MRD assessment is gradually transforming patient management strategies. 03 《肿瘤瞭望-泌尿时讯》 目前已有不少膀胱保留疗法的临床研究见诸报道，但尚缺乏足以改变临床实践的有力证据。您认为当前验证膀胱保留策略的临床试验设计存在哪些主要局限？应如何优化？ Andrea Necchi 教授 Vita-Salute San Raffaele大学 当前膀胱保留策略通常先对符合条件的患者进行全身治疗，再依据疗效决定膀胱处理方式。多项临床试验表明，对于达到深度缓解并成功保膀胱的患者，即使后续接受维持免疫治疗或主动监测，仍可能出现膀胱内复发，且以高级别非肌层浸润性复发为主。 RETAIN研究是一项前瞻性、多中心的II期临床试验，旨在评估对肌层浸润性膀胱癌患者采用剂量密集型MVAC新辅助化疗后，进行主动监测而非立即进行根治性膀胱切除术的膀胱保留策略的可行性和疗效。结果显示，在达到临床完全缓解并选择主动监测的患者中，研究成功实现了较高的短期膀胱保留率。但仍有部分患者出现复发。尽管大部分复发局限于膀胱内（非肌层浸润性），但其中存在一定比例的患者最终进展为转移性疾病。这揭示了当前膀胱保留策略的一个核心挑战：即使对初步治疗反应良好，且复发局限于膀胱的患者，高级别复发本身可能预示着潜在的侵袭性生物学行为，存在转移风险。现有的临床评估手段（如影像学和膀胱镜复查）可能不足以精准识别出那些即使达到临床完全缓解，但远期转移风险依然较高的患者。目前临床上缺乏能够在个体层面精准预测膀胱内复发风险的工具。常规MRD评估方法（如ctDNA）对检测微小膀胱内复发的灵敏度可能不足，utDNA或许更具潜力，但仍需进一步数据验证。 因此，未来临床试验应从两方面加以改进：一是优化患者筛选策略，引入utDNA等更灵敏的生物标志物以提升复发风险预测能力；二是在全身治疗有效的背景下，探索加强膀胱局部治疗的方式，如采用新型膀胱内药物灌注或放疗等手段，以期降低膀胱内复发率，从而提高保膀胱策略的整体成功率与安全性。 上下滑动查看英文对话 Oncology Frontier- UroStream: Many clinical studies on bladder preservation have been reported, but there is still a lack of compelling evidence sufficient to change clinical practice. What do you believe are the primary limitations of current clinical trial designs for bladder preservation, and how should they be optimized? Dr. Necchi：Current bladder preservation strategies typically involve systemic therapy for eligible patients, followed by a decision on bladder management based on efficacy. Multiple clinical trials have shown that even for patients who achieve deep remission and successfully retain their bladder, intravesical recurrence remains possible—primarily as high-grade non-muscle invasive recurrence—despite subsequent maintenance immunotherapy or active surveillance. The RETAIN study was a prospective, multicenter Phase II clinical trial designed to evaluate the feasibility and efficacy of an active surveillance strategy instead of immediate radical cystectomy for MIBC patients following dose-dense MVAC (ddMVAC) neoadjuvant chemotherapy. The results showed that among patients who achieved cCR and chose active surveillance, the study successfully achieved high short-term bladder preservation rates. However, recurrences still occurred in some patients. While most recurrences were localized to the bladder (non-muscle invasive), a certain proportion of these patients eventually progressed to metastatic disease. This reveals a core challenge: even in patients with a good initial response whose recurrence is localized to the bladder, high-grade recurrence itself may indicate aggressive underlying biology and a risk of metastasis. Existing clinical assessment tools (such as imaging and cystoscopic follow-up) may be insufficient to accurately identify patients who, despite reaching cCR, still face a high risk of long-term metastasis. Currently, we lack tools to precisely predict the risk of intravesical recurrence at the individual level. The sensitivity of conventional MRD methods (like ctDNA) for detecting minute intravesical recurrences may be inadequate; utDNA may hold more potential, though further data validation is required. Consequently, future clinical trials should be improved in two areas: Optimizing patient screening strategies: Incorporating more sensitive biomarkers like utDNA to enhance recurrence risk prediction.Strengthening local consolidation: In the context of effective systemic therapy, exploring ways to reinforce local bladder treatment—such as through novel intravesical drug instillations or radiotherapy—to reduce intravesical recurrence rates and improve the overall success and safety of bladder preservation strategies。 Andrea Necchi 教授 意大利Vita-Salute San Raffaele大学泌尿生殖系统肿瘤中心主任 Andrea Necchi教授是一名专攻泌尿系统恶性肿瘤治疗的肿瘤内科医生，在米兰圣拉斐尔科学研究医院担任泌尿生殖系统肿瘤内科负责人，还是圣拉斐尔生命健康大学（UniSR）的肿瘤学副教授。 Necchi教授先后在米兰大学获得医学学位和肿瘤内科博士后专业学位。Necchi教授自作为医学生接受临床培训以来一直就职于意大利国家癌症研究所基金会（位于意大利米兰），2020年11月开始在圣拉斐尔科学研究医院执业。 Necchi教授主要从事泌尿生殖系统恶性肿瘤的治疗工作。其研究团队专注于泌尿系统恶性肿瘤的全部领域，主要致力于新试验性治疗的全阶段临床试验研发。Necchi教授近期的工作重点是制定在可手术治疗疾病的早期引入新疗法联合根治性手术的围手术期策略。 （来源：《肿瘤瞭望-泌尿时讯》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。

The $318 million proceeds make Aktis a larger IPO than any of the handful of biotech offerings last year.\n Aktis Oncology exceeded its own expectations for its IPO in a good omen for those hoping for a more inviting public market this year.The company, which has accrued an impressive list of Big Pharma backers in its previous funding rounds, estimated earlier this week that it would sell 11.8 million shares priced between $16 and $18 apiece. But the IPO this morning sees the biotech reach the top end of the price range while bumping up the number of shares to 17.6 million.The recalibrated figures mean the IPO should bring in gross proceeds of about $318 million—significantly above the net proceeds of $181.7 million the company had predicted Monday.The proceeds could rise by another $47.6 million if underwriters take up their 30-day offer to buy an additional 2.6 million shares at the same price of $18. The previous expectation was that Aktis would only offer 1.7 million shares to underwriters.Aktis’ shares are due to start trading on the Nasdaq Friday morning under the ticker “AKTS.”The $318 million proceeds make the biotech a larger IPO than any of the handful of biotech offerings last year—beating obesity biotech Metsera’s $275 million, LB Pharmaceuticals’ $285 million or MapLight Therapeutics’ $250 million IPOs.In its filing on Monday, Aktis explained how it had earmarked between $140 million and $150 million of the proceeds to fund the ongoing U.S. phase 1b study of the miniprotein radiopharmaceutical Ac-AKY-1189 for Nectin-4 expressing tumors. Preliminary results from the dose-escalation portion of the study are expected to read out in the first quarter of 2027. Aktis has previously pointed out that Pfizer and Astellas\' Padcev, an antibody-drug conjugate that also targets Nectin-4, brought in worldwide sales of $1.9 billion in 2024. Aktis has argued that Padcev has had “limited” impact beyond urothelial cancer due to the need to develop a companion diagnostic.The biotech is hoping to carve out its own niche for Ac-AKY-1189 by using imaging radioisotopes conjugated to the drug to select patients most likely to benefit from the treatment.Meanwhile, another $70 million to $80 million of the IPO proceeds is expected to fund the launch a phase 1b study of its second asset, Ac-AKY-2519, for B7-H3 expressing tumors, according to Monday’s filing.Aktis oversaw 76 full-time employees as of September 2025, who are based across a site in Boston and another in Durham, North Carolina. The company, which ended September with $246.2 million still in the bank, has previously said it expects the IPO proceeds will help keep the company financed until the first half of 2028.The biotech saw the likes of Bristol Myers Squibb and Merck & Co.’s MRL Ventures Fund join previous backer Eli Lilly for a $175 million series B last year. The pharma attention was based on Aktis’ platform for delivering alpha emitters to cancer cells using miniproteins, an approach that could potentially destroy tumors without causing intolerable harm to healthy tissues.Aktis’ upsized IPO backs up industry observers’ predictions to Fierce that the IPO window could reopen in 2026—although no other biotechs have yet confirmed they will be following Aktis’ lead this year.