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点击蓝字，关注我们 编者按：尿路上皮癌（UC）是一种具有侵袭性的恶性肿瘤，其发病率高且并发症严重。近年来，学术界对该疾病的认识及治疗均取得了重大进展，尤其是免疫检查点抑制剂、靶向治疗、抗体偶联药物等新型疗法拓展了应用范围。近期，素有“神刊”之称的《临床医师癌症杂志》（CA A Cancer J Clinicians，2025年最新IF=232.4）发表了一篇尿路上皮癌围术期治疗的综述。本文整理了膀胱癌领域的重要研究进展和作者观点。 一、肌层浸润性膀胱癌（MIBC） 01 免疫治疗 MIBC的治疗格局正在由“全切”向“精准保留”演进。围术期免疫治疗已不再局限于术后辅助。CheckMate 274率先证实，根治性膀胱切除后给予PD-1抑制剂纳武利尤单抗可将中位无病生存期从10.8个月延长到20.8个月，基于此，FDA把“观察等待”改写为“标准辅助治疗”。随后，NIAGARA研究把免疫治疗药物前移到术前，形成化疗＋度伐利尤单抗“夹心”方案，两年无事件生存率升至67.8%，总生存率82.2%，正式奠定了围术期免疫联合化疗的新基准。 对于顺铂不耐受人群，单药新辅助免疫治疗仍属探索研究阶段，PURE-01研究中帕博利珠单抗单药治疗的病理完全缓解（pCR）率虽达42%，但尚缺III期生存数据，因此仅作为临床试验或特定患者的治疗选择。 表1. 已完成或在研的MIBC围术期治疗研究 02 抗体偶联药物（ADC）治疗 “魔法子弹”ADC的崛起进一步拓宽了武器库。靶向nectin-4的维恩妥尤单抗（Enfortumab vedotin，EV）在EV-103研究中用于顺铂不耐受患者，病理完全缓解率36%，一年无事件生存76.4%，且手术未因毒性延迟；EV-302研究中，EV与帕博利珠单抗联用后，客观缓解率（ORR）突破70%，已被NCCN治疗列为顺铂不耐受人群的一线治疗首选方案。 靶向HER2的德曲妥珠单抗（Trastuzumab deruxtecan，T-DXd）则在DESTINY-PanTumor02中显示，HER2 3＋膀胱癌亚组客观缓解率56.3%，中位生存13.4个月，FDA已加速批准其用于既往经治、无替代方案的HER2阳性实体瘤。这些ADC正在向围术期推进，而KEYNOTE-905/EV-303、KEYNOTE-B15/EV-304等III期研究正在验证EV联合免疫能否取代传统化疗。 03 MIBC保膀胱治疗 在“保膀胱”策略方面，根治性膀胱切除不再是唯一答案。三联疗法（TMT）——最大程度经尿道电切＋同步放化疗——的长期随访显示，五年肿瘤特异生存83%，与根治术相当，且生活质量显著优于切除组；RTOG系列试验汇总468例患者，十年总生存率36%，仅21%最终需挽救性膀胱切除。针对顺铂不耐受者，RTOG 0712提示低剂量吉西他滨同步放疗的三年膀胱保存率与含顺铂方案相似（72% vs 67%）。 免疫能否再提升TMT疗效？正在进行的NRG-GU005将同步放化疗与放化疗＋阿替利珠单抗进行头对头比较，结果备受期待。此外，研究者尝试用生物标志物“筛选”可保膀胱人群：RETAIN研究在DNA损伤修复基因突变且化疗后≤T1的患者中，48%得以避免手术且两年无转移生存76%，提示基因指导的个体化保膀胱策略已初现雏形。 04 新型诊断标志物 精准治疗需要精准监测。循环肿瘤DNA（ctDNA）可在术前预判病理完全缓解：Dyrskjøt等发现术前ctDNA阴性者pCR概率显著升高，ctDNA清除程度与复发风险呈梯度相关；IMvigor010子研究亦显示，术后ctDNA阳性人群可从辅助阿替利珠单抗显著获益（HR 0.58）。ctDNA因而有望成为“是否免切膀胱”及“是否加强辅助”的动态决策工具。血清irisin和CYR61蛋白亦被报道分别可用于区分MIBC与NMIBC，但尚需外部验证。 05 新型预后标志物 在预后层面，TIGIT/PD-1共表达谱可把肿瘤微环境分为三群：TIGIT高表达者虽总体预后最差，却对辅助化疗＋PD-L1抑制最敏感，提示联合免疫方案的选择可依据微环境分型。全基因组DNA甲基化评分在413例MIBC中独立于T/N分期预测3年及5年死亡风险，或可成为术前风险分层的新尺子。尿液PD-L1（uPD-L1）水平升高与更短的无复发生存相关，虽尚未达统计学意义，但为非侵入性监测提供了新思路。 二、非肌层浸润性膀胱癌（NMIBC） 01 卡介苗无反应的NMIBC的治疗选择 NMIBC治疗最大的痛点是卡介苗（BCG）无反应人群。国际共识定义“BCG无反应”为完成足量BCG后12个月内持续/复发原位癌，或6个月内复发高级别乳头状瘤。约三分之一患者陷入此困境，传统方案唯有膀胱切除。 近年来，FDA先后批准nadofaragene firadenovec（重组干扰素α2b基因疗法）、N-803（IL-15超激动剂联合BCG）及帕博利珠单抗（PD-1抑制剂）用于BCG无反应原位癌，完全缓解率分别达53%、71%和41%，且2年膀胱保存率约50%。此外，回顾性数据提示序贯吉西他滨＋多西他赛膀胱灌注的1年无高级别复发率65%，2年49%，仅20%患者最终需切除，为不愿或不能手术者提供了有效替代。正在进行的BRIDGE研究将比较BCG与吉西他滨/多西他赛在BCG初治高危NMIBC中的疗效，2029年将给出答案。 表2. 已完成或在研的NMIBC围术期治疗研究 02 试验设计中需要更好的基于尿液的监测指标 试验设计的另一痛点是随访方式。现行指南推荐的膀胱癌随访策略仍以频繁膀胱镜＋随机活检为主，既增加患者负担又容易导致过度检查。Cxbladder Monitor等尿液mRNA检测已显示阴性预测值100%，有望减少50%以上镜检，却仍被多数试验忽略。国际膀胱癌小组呼吁未来的临床试验以无复发生存（RFS）为主要终点，并以无创尿液指标作为次要终点，以降低受试者毒性和成本。 03 通过不同的组织学更好地理解风险 组织学异质性也可影响治疗选择。临床中，大约有超过25%的NMIBC伴变异形态，其中微乳头、浆细胞样、神经内分泌等亚型进展风险极高。大样本回顾性分析提示，对微乳头型而言，即刻根治切除与保膀胱治疗五年生存无差异（43.9% vs 53.2%）；而肉瘤样、鳞样、腺样及神经内分泌型则明显受益于早期手术（31.9%–44.0% vs 19.9%–23.3%）。因此，识别变异亚型不仅有助于预后评估，而且可指导手术“切”与“不切”的决策。 04 NMIBC背景下的保膀胱策略和三联疗法 TNT已经在MIBC保膀胱治疗中越来越广泛的应用，对于需要保膀胱的高危NMIBC也有一定的借鉴价值。RTOG 0926在BCG失败的高级别T1患者中采用放疗＋化疗（顺铂或丝裂霉素/5-FU）＋重复电切，三年膀胱保存率88%，五年总生存56%，证实TMT可作为BCG失败后的补救策略。McElree等报道的序贯吉西他滨/卡巴他赛＋静脉pembrolizumab方案，使77%病灶在一年内维持完全缓解，提示在免疫时代，保膀胱策略已从MIBC扩展到NMIBC。 三、膀胱切除术的考量及术后康复的改进 01 淋巴结清扫的作用和范围 根治性膀胱切除仍是多数肌层浸润或高危NMIBC的终极方案，但手术范围、患者个体化及术后康复正被重新改写。淋巴结清扫历来被视为切除“越多越好”，SWOG S1011随机研究却给出警示：与标准清扫相比，扩大清扫未带来生存获益，反而使3–4级并发症升至16%，90天死亡率达5.5%。然而，荟萃分析提示在高复发病例中扩大清扫仍可改善无复发生存，因此建议仅对影像或术中提示高危淋巴结转移者行扩大清扫。 02 女性患者膀胱切除术的注意事项 女性患者常被“一刀切”地切除子宫、阴道前壁和附件。两项多中心回顾性研究却显示，85%以上女性实际并无生殖道受累，保留子宫及阴道对切缘阳性率、复发及生存均无负面影响；而问卷调查显示77%女性认为阴道保留“极重要”，但仅不足三成术前接受充分性功能咨询。因此，指南推荐：肿瘤未累及膀胱颈/三角区时，可行神经及生殖道保留；若必须切除，可考虑带蒂皮瓣或肠段阴道重建，以维持性功能和身体意象。 图1.男性和女性盆腔解剖分离模型示意图：(A) 男性膀胱背侧、前列腺背侧与精囊腺前壁之间的解剖平面。该层面需精确分离，以避免损伤走行于前列腺外侧的神经血管束。膀胱壁、精囊腺与前列腺基底之间的关键解剖夹角。精囊腺（SV）腹侧平面的分离应避免损伤位于精囊背外侧的盆腔神经血管丛。(B) 女性膀胱背侧与子宫-宫颈前壁之间的解剖平面。该层面需精确分离，以避免损伤走行于阴道旁间隙腹外侧的神经血管束。膀胱三角区、阴道侧壁与子宫颈之间的关键解剖夹角。沿阴道旁间隙腹外侧平面进行的分离路径（根据Studer 2015修改） 03 老年患者膀胱切除术的注意事项 年龄不应成为手术的绝对禁忌，但患者的身体状态应该得到更加科学的量化。有研究显示，70岁以上患者术后30天内严重并发症可达49%，死亡率4%，几乎两倍于普通人群。综合老年评估（CGA）可提前发现认知、营养、用药等隐患，GERICO试点项目证实，≥75岁患者经CGA协同管理后，61%每日接受老年科访视，无一人因评估延迟手术。预康复（prehabilitation）结合营养、运动和心理干预显示，依从≥80%者术后并发症减少、功能恢复更快。Fried衰弱量表、计时起立行走等简易工具已被证实可预测30–90天并发症，应在术前常规应用。 04 膀胱切除术后的加速康复（ERAS） 通过多环节干预的术后ERAS可显著缩短患者的住院及功能恢复时间。中国多中心RCT证实，ERAS可使术后排气时间缩短1.5天、住院时间由12天减至7天，而不增加并发症。然而，关于长期肿瘤结局的结论不一：一项2111例大样本回顾分析提示ERAS与对照组的五年肿瘤特异生存无差异；而另一项单中心前瞻性研究却显示ERAS组五年总生存（67% vs 36%）和癌症特异生存（74% vs 48%）均显著提高。提示ERAS至少不损及肿瘤安全性，且可能通过减少并发症间接改善生存。未来需设计良好的随机研究以确定ERAS对肿瘤学结局的真正影响。 综上所述，无论是MIBC还是NMIBC，围术期管理正走向“精准分层、器官优先、功能保护、协同康复”的新阶段。多学科团队应综合分子特征、组织学亚型、患者脆弱程度及个人意愿，为每一位患者量身定制“从头到脚”的全程策略。 ▌参考文献： Yip W, Jaime-Casas S, Kothari A, et al. Urothelial carcinoma: Perioperative considerations from top to bottom. CA Cancer J Clin. Published online June 6, 2025. doi:10.3322/caac.70019 （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。

CULVER CITY, Calif.--(BUSINESS WIRE)--ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, today announced preliminary financial results for the fiscal quarter ended June 30, 2025, and clinical progress across its pipeline. Key Highlights Q2 2025 Revenue Growth with Continued Strong Sales Momentum : $26.4 million, up 60% from Q1 2025, with year-to-date sales of ~$43 million. ANKTIVA ® Unit Growth Since J-Code: 246% unit sales volume growth in 1H 2025 compared to 2H 2024. Cash Position : $153.7 million in cash, cash equivalents and marketable securities as of June 30, 2025. NSCLC : Initiated randomized clinical trial (RCT) ResQ201A with N-803 + tislelizumab in 2 nd line lung cancer; US sites initiated, submitted clinical trial applications in EU, UK; Canada and Asia filings planned. Lymphopenia : FDA supportive of new data; reaffirmed RMAT/EAP; collaborative discussion outlining regulatory endpoints, trial design and registrational pathways to full approval for the treatment of lymphopenia with randomized trial design in progress. Full Enrollment Reached in the Randomized NCI Cancer Prevention Clinical Trial Using ANKTIVA + Adenovirus Vaccine in 186 Patients with Lynch Syndrome. United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) marketing authorization application of ANKTIVA approved. Papillary NMIBC : Discussion with FDA regarding filing status of supplemental BLA. ImmunityBio performing ongoing evaluation of next steps to address the Refuse to File decision by the FDA, following June Type A meeting with the Agency. New updated data on Papillary disease provided to the FDA and discussions with Agency to continue. Separately, ImmunityBio has applied to the National Comprehensive Cancer Network (NCCN) to seek expansion of the BCG-unresponsive NMIBC guidelines to include papillary-only disease. Financial Overview In the second quarter of 2025, ImmunityBio reported $26.4 million in revenue, representing a 60% increase from $16.5 million in the first quarter of 2025. This growth reflects continued commercial traction of ANKTIVA + BCG in BCG-unresponsive non-muscle invasive bladder cancer with CIS with or without Papillary tumors. The 1H 2025 sales of $42.9 million represents a 246% increase in unit volume during the first two quarters of 2025 since the J-code approval versus the last two quarters of 2024. The Company ended the quarter with $153.7 million in cash, cash equivalents and marketable securities as of June 30, 2025. Non-Muscle Invasive Bladder Cancer (Papillary NMIBC) ImmunityBio conducted a Type A meeting with the FDA in June to discuss its program targeting papillary-only NMIBC and the Agency’s response to the supplemental BLA filing. Contrary to the advice the FDA gave the Company in January 2025 to submit the supplemental BLA, the FDA responded with a Refuse-to-File (RTF) notice in May on the basis of requiring a randomized controlled trial (RCT) against chemotherapy. At the June meeting, ImmunityBio provided new data regarding the updated results since the initial BLA filing of papillary only data as well as real-world data of chemotherapy just published in this indication. In the papillary only NMIBC new data based on 26 of the 100 subjects in Cohort A and 80 subjects in Cohort B (Papillary Alone) of our QUILT-3.032 trial, demonstrated long-term (36-month) progression free survival and bladder sparing with ANKTIVA + BCG. ImmunityBio presented the newly published real-world data which demonstrates that compared to chemotherapy, ANKTIVA + BCG led to improved outcomes of progression free survival and cystectomy avoidance at 36-months. To our knowledge, the results to date of ANKTIVA + BCG represent the longest duration of follow-up with the longest duration of bladder sparing in these subjects. The Company indicated at the meeting that it would seek a new meeting request with this new data and withdraw the prior supplemental BLA filing; however, the Company is re-evaluating this approach in consultation with its regulatory counsel and may seek to amend the initial filing with the new data rather than withdrawing it, with a commitment to initiate a randomized controlled trial of chemotherapy free ANKTIVA + BCG versus chemotherapy in the papillary alone indication. Separately, ImmunityBio has applied to the National Comprehensive Cancer Network (NCCN) to seek expansion of the BCG-unresponsive NMIBC guidelines to include papillary-only disease, in addition to the currently recognized CIS with or without papillary disease. The NCCN is expected to review the submission at its August 2025 meeting. Non-Small Cell Lung Cancer (NSCLC) ImmunityBio has launched ResQ201A, a randomized controlled trial, in the United States, evaluating its IL-15 superagonist N-803 in combination with tislelizumab, a PD-1 checkpoint inhibitor from BeOne Medicines in patients with 2nd line lung cancer who were progressing on checkpoint inhibitors. The Company has also submitted clinical trial applications for ResQ201A in the European Union and the United Kingdom, with Canada expected to be submitted in early Q3 2025, and with plans underway to submit in Asia. Lymphopenia The Company also met with the Division of Non-Malignant Hematology at the FDA in June to present updated data from its lymphopenia program. The Division was supportive of the findings including the underlying science of stimulating lymphocytes with ANKTIVA and expressed a desire to support an efficient path to approval, noting that additional time will be required to finalize the appropriate development plan. Expanded Access Program (EAP) authorization has been activated for the indication for all solid tumors in patients who have failed first-line treatment on chemotherapy, radiotherapy or immunotherapy and exhibit low Absolute Lymphocyte Counts (ALC < 1,000/μL). Disclaimer Regarding Financial Overview The information and amounts presented above, including under the caption “Financial Overview,” reflects the Company’s preliminary estimates based solely upon information available to it as of the date of this press release, and the amounts reported are not a comprehensive statement of its financial results or position as of June 30, 2025. Any actual amount that the Company reports in its Quarterly Report on Form 10-Q for the period ended June 30, 2025 will be subject to its financial closing procedures and any final adjustments that may be made prior to the time its financial results for the period ended June 30, 2025 are finalized. As a result, these preliminary estimates may differ materially from the actual results that will be reflected in the Company’s condensed consolidated financial statements for the quarter when they are completed and publicly disclosed. About ANKTIVA The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo. ANKTIVA was approved by the FDA in 2024 and by UK MHRA in 2025 for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors. For more information, visit Anktiva.com. About ImmunityBio ImmunityBio is a vertically-integrated commercial stage biotechnology company developing next-generation therapies that bolster the natural immune system to defeat cancers and infectious diseases. The Company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. Designated an FDA Breakthrough Therapy, ANKTIVA is the first FDA-approved immunotherapy for non-muscle invasive bladder cancer CIS that activates natural killer cells, T cells, and memory T cells for a long-duration response. The Company is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases. For more information, visit ImmunityBio.com (Founder’s Vision) and connect with us on X (Twitter), Facebook, LinkedIn, and Instagram. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding discussions and meetings with the U.S. FDA, including with respect to the previously reported RTF letter received by the Company and potential implications thereof, potential next steps, decisions and timeline related to the Company’s regulatory submissions and strategy, financial results anticipated to be reported in future SEC filings, clinical trial data and potential results and implications to be drawn therefrom, the expectation that the EAP described herein will enable patients to have access to ANKTIVA for the indication described, the RMAT designation as previously reported and potential results therefrom and regulatory submissions in connection therewith, the belief that ALC levels and NLR levels obtained from a CBC are predictors of clinical benefit and outcomes relating to overall survival, clinical trial and expanded access program enrollment, timing, data and potential results to be drawn therefrom, anticipated components of ImmunityBio’s Cancer BioShieldTM platform, anticipated review timeline for the Company’s NCCN guidelines submission in NMIBC papillary only and potential implications therefrom, the development of therapeutics for cancer and infectious diseases, potential benefits to patients, potential treatment outcomes for patients, the described mechanism of action and results and contributions therefrom, potential future uses and applications of ANKTIVA alone or in combination with other therapeutic agents for the prevention or reversal of lymphopenia, potential future uses and applications of ANKTIVA alone or in combination with other therapeutic agents across multiple tumor types and indications and for potential applications beyond oncology, potential regulatory pathways and the regulatory review process and timing thereof, the application of the Company’s science and platforms to treat cancers or develop cancer vaccines, immunotherapies and cell therapies that have the potential to change the paradigm in cancer care, and ImmunityBio’s approved product and investigational agents as compared to existing treatment options, among others. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “goal,” “could,” “estimates,” “scheduled,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “is,” “seeks,” “should,” “will,” “strategy,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to ImmunityBio. Such information may be limited or incomplete, and ImmunityBio’s statements should not be read to indicate that it has conducted a thorough inquiry into, or review of, all potentially available relevant information. Such statements reflect the current views of ImmunityBio with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about ImmunityBio, including, without limitation, (i) risks and uncertainties regarding the FDA regulatory submission, filing and review process and the timing thereof, (ii) whether the RMAT designation will lead to an accelerated review or approval, of which there can be no assurance, (iii) risks and uncertainties regarding commercial launch execution, success and timing, (iv) risks and uncertainties regarding participation and enrollment and potential results from the expanded access clinical investigation program described herein, (v) whether clinical trials will result in registrational pathways and the risks, (vi) whether clinical trial data will be accepted by regulatory agencies, (vii) the ability of ImmunityBio to continue its planned preclinical and clinical development of its development programs through itself and/or its investigators, and the timing and success of any such continued preclinical and clinical development, patient enrollment and planned regulatory submissions, (viii) potential delays in product availability and regulatory approvals, (ix) ImmunityBio’s ability to retain and hire key personnel, (x) ImmunityBio’s ability to obtain additional financing to fund its operations and complete the development and commercialization of its various product candidates, (xi) potential product shortages or manufacturing disruptions that may impact the availability and timing of product, (xii) ImmunityBio’s ability to successfully commercialize its approved product and product candidates, (xiii) ImmunityBio’s ability to scale its manufacturing and commercial supply operations for its approved product and future approved products, (xiv) whether the NCCN will review and/or approve the Company’s submission described herein on the anticipated timeline or at all, and (xv) ImmunityBio’s ability to obtain, maintain, protect, and enforce patent protection and other proprietary rights for its product candidates and technologies. More details about these and other risks that may impact ImmunityBio’s business are described under the heading “Risk Factors” in the Company’s Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 3, 2025, and the Company’s Form 10-Q filed with the SEC on May 12, 2025, and in subsequent filings made by ImmunityBio with the SEC, which are available on the SEC’s website at www.sec.gov. ImmunityBio cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof.