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III 期 CREST 研究结果显示，与单独使用标准治疗相比，Sasanlimab 联合卡介苗（BCG）膀胱灌注治疗，可使疾病相关事件（包括高级别疾病复发或进展等）风险降低 32%皮下注射 PD-1 抑制剂Sasanlimab联合卡介苗治疗既往未接受过卡介苗治疗的高危非肌层浸润性膀胱癌患者，有望成为 30 余年来该治疗领域的首个突破性进展相关研究结果已提交至全球卫生监管机构，以支持潜在的注册申报辉瑞公司4月26日宣布，针对其在研创新药Sasanlimab的关键性III期CREST临床试验达到主要研究终点。Sasanlimab是一款皮下注射PD-1单抗（mAb），该研究旨在评估Sasanlimab联合标准治疗（SOC）卡介苗（BCG）诱导伴或不伴维持治疗，在既往未接受过卡介苗治疗的高危非肌层浸润性膀胱癌（NMIBC）患者中的疗效，试验已达到主要终点，即研究者评估的无事件生存期（EFS）。与单独使用卡介苗（诱导伴维持）治疗相比，Sasanlimab与卡介苗（诱导伴维持）的联合治疗方案显示出具有临床意义且统计学显著的无事件生存期（EFS）改善：风险比(HR)为0.68; 95%置信区间（CI），0.49-0.94；双臂p值=0.019；中位无事件生存期（mEFS）尚未达到。研究显示，相比对照组，联合治疗方案可将疾病相关事件（包括高级别疾病复发或进展）风险降低32%。在预设的更高风险患者亚组中，联合治疗组在无事件生存期方面均展现出一致的获益，其中T1期患者的无事件生存期风险比（HR）为0.63 (0.41, 0.96) ，伴有原位癌（CIS）的患者无事件生存期风险比（HR）为0.53 (0.29, 0.98)。无事件生存期（EFS）是一个复合终点，指从随机分组到首次出现高级别疾病复发、疾病进展、原位癌持续存在或因任何原因导致的死亡等事件的时间。在接受 Sasanlimab 联合卡介苗（诱导伴维持）治疗的患者中，在第36 个月时无事件生存率为 82.1%（95% CI, 77.4-85.9）；而在仅接受卡介苗（诱导伴维持）治疗的患者中，这一比例为 74.8% (95% CI, 69.7-79.2)。CREST 研究结果已于4月26日-29日举行的 2025 年美国泌尿外科协会（AUA）年会期间，在全体大会口头报告环节公布。“长期以来，膀胱癌的临床治疗亟需能够降低疾病复发和进展风险的创新方案。几十年来，卡介苗膀胱灌注免疫治疗都是肿块切除术后的标准治疗方案，但仍有高达50%的高危非肌层浸润性膀胱癌（NMIBC）患者治疗失败。”卡罗莱纳泌尿外科研究中心医学主任、CREST试验主要研究者、美国外科医师学会(FACS)会员Neal Shore博士表示，"CREST III期研究结果表明，在疾病早期阶段将Sasanlimab联合卡介苗（诱导伴维持）作为治疗方案，能够显著延长患者的无事件生存期，显示出联合治疗方案在重塑膀胱癌临床治疗格局、减轻患者疾病负担方面的潜力与价值。"膀胱癌是全球第九大癌症，每年约造成22 万人死亡1,2。其中，非肌层浸润性膀胱癌约占所有膀胱癌的 75%3。尽管卡介苗治疗已证实可降低肿瘤复发风险，但是40%-50%的高危非肌层浸润性膀胱癌患者在接受这一治疗后，仍会出现疾病复发或进展4-6。“最新的关键性 III 期 CREST 试验结果为膀胱癌患者带来了期待已久的治疗突破。作为三十多年来首个与卡介苗联用的免疫治疗，Sasanlimab能为既往未接受过卡介苗治疗的高危非肌层浸润性膀胱癌患者带来显著获益。” 辉瑞肿瘤事业部首席开发官 、Megan O’Meara博士表示，“CREST的研究结果对早期膀胱癌患者意义重大，皮下注射的免疫检查点抑制剂能有效延缓疾病复发或进展，帮助这类患者从创新治疗方案中得到更多生存获益。这些研究结果也进一步彰显了辉瑞对处于不同疾病进展阶段的膀胱癌患者的长期承诺。我们期待与全球监管机构合作，让Sasanlimab成为高危非肌层浸润性膀胱癌的重要治疗选择。”在关键次要终点分析中，与单独使用卡介苗诱导伴维持治疗相比，Sasanlimab 联合卡介苗（仅诱导）治疗，未能延长无事件生存期（EFS）：风险比(HR)为1.16；95%置信区间（CI），0.87-1.55；双臂p值=0.312。这一结果显示，卡介苗维持治疗不仅是标准治疗方案的一部分，也是联合Sasanlimab治疗的关键组成部分。针对另一关键次要终点总生存期（OS），较早的中期分析显示，在中位随访40.9个月时，各治疗组之间尚未观察到差异。该研究将继续进行生存随访，并在最终分析中对OS进行评估。对于在随机分组时伴有原位癌的患者，完全缓解率（CR）及其持续缓解时间是研究设定的额外次要终点。分析结果显示，Sasanlimab联合卡介苗诱导伴维持治疗组与单独使用卡介苗诱导伴维持治疗组在任何时间点达到的完全缓解率分别为89.8%和 85.2 %。值得注意的是，对于在随机分组时伴有原位癌的患者中，在第36个月时，Sasanlimab联合治疗组中仍然有91.7%保持完全缓解，而在单独使用卡介苗治疗组中，这一数字为67.7%。Sasanlimab联合卡介苗治疗的总体安全性表现与已知的卡介苗安全性表现以及Sasanlimab在临床试验中报告的数据一致。Sasanlimab的安全性表现也与已公布的PD-1抑制剂安全性表现相一致。辉瑞已将相关数据提交至全球卫生监管机构，以支持潜在的注册申报。关于CREST滑动阅览CREST 试验是一项 III期、国际多中心、随机、开放性、三个平行组研究，旨在评估PD-1 单抗Sasanlimab联合卡介苗（BCG）（BCG诱导伴或不伴维持）治疗，与单独使用卡介苗（BCG）（诱导伴维持）治疗相比，在既往未接受卡介苗（BCG）治疗的高危非肌层浸润性膀胱癌（NMIBC）患者中的疗效。患者被随机分配接受以下几种治疗：每四周皮下（SC）注射一次 300毫克Sasanlimab，最多注射 25 个周期（一个周期为四周），同时联合卡介苗每周一次连续六周（诱导期），之后进行（A 组；n=352）或不进行（B 组，n=352）卡介苗（BCG）维持治疗；或者仅接受卡介苗（BCG）诱导伴维持治疗直至 25 个周期（C 组，n=351）。主要终点是由研究者评估的 A 组和 C 组之间的无事件生存期（EFS），作为复合终点定义为从随机分组到首次出现高级别疾病复发、疾病进展、原位癌（CIS）持续存在、任何原因导致的死亡任一事件的时间。关键次要终点包括由研究者评估的 B 组和 C 组之间的无事件生存期（EFS），A/B 组与 C 组之间的 OS。在伴有原位癌（CIS）的患者中，完全缓解率（CR）及其持续时间是额外次要终点。有关 CREST 试验的更多信息（NCT04165317），请访问 www.clinicaltrials.gov。关于 Sasanlimab滑动阅览Sasanlimab是一种人源化免疫球蛋白G4（IgG4）单克隆抗体，通过与人PD- 1受体的高亲和力结合，阻断与 PD-1 和 PD-L1/PD-L2 的相互作用。PD-1 是一种在 T 细胞、树突状细胞、自然杀伤细胞、巨噬细胞和 B 细胞上表达的蛋白质，作为免疫检查点，当其配体激活时，能够负向调节 T 细胞的激活和效应功能，并可能在肿瘤逃逸宿主免疫过程中发挥重要作用。Sasanlimab 可以通过每四周一次的皮下注射（2 毫升）给药。在早期临床研究中，每四周皮下注射 300 毫克的 Sasanlimab 在晚期实体瘤和晚期尿路上皮癌中显示出临床疗效。除了用于非肌层浸润性膀胱癌（NMIBC），Sasanlimab与辉瑞的抗体偶联物（ADC）的联合疗法也正在进行多项临床研究。关于辉瑞肿瘤滑动阅览在辉瑞肿瘤，我们身处癌症治疗新纪元的最前沿。我们拥有行业领先的产品组合和广泛的产品管线，聚焦小分子药物、抗体偶联药物（ADC）、双特异性抗体等免疫疗法三个核心作用机制、从多个方向着手攻克癌症。我们致力于为乳腺癌、泌尿系统肿瘤、血液肿瘤、消化道肿瘤、妇科肿瘤和包括肺癌在内的胸部肿瘤等全球高发癌种提供变革性的治疗方案。在科学的驱动下，辉瑞致力于加快突破性创新的步伐，帮助肿瘤患者延长生命、改善生活质量。关于辉瑞：为患者带来改变其生活的突破创新滑动阅览在辉瑞，我们通过科学和全球资源为人们提供治疗方案，以延长其生命，显著改善其生活。在医疗卫生产品的探索、研发和生产过程中，辉瑞始终致力于奉行严格的质量、安全和价值标准。我们在全球的产品组合包括创新药品和疫苗。每天，辉瑞在发达和新兴市场的员工都在推进人类健康，推动疾病的预防、治疗和治愈，以应对挑战我们这个时代的顽疾。辉瑞还与医疗卫生服务方、政府和社区合作，支持并促进世界各地的人们能够获得更为可靠和可承付的医疗卫生服务。这与辉瑞作为一家全球卓越的创新生物制药公司的责任是一致的。175年来，辉瑞一直致力于为所有依赖我们的人带来改变。如需了解更多信息，请登录www.pfizer.com.cn。免责声明：本新闻稿仅在于传递科学前沿信息，不构成对任何药物或治疗方案的推荐或推广。如您有药物或治疗方面的问题，请咨询医疗卫生专业人士。滑动查看1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263.2. Bladder cancer statistics. World Cancer Research Fund International. Accessed March 20, 2025. https://www.wcrf.org/cancer-trends/bladder-cancer-statistics/ 3. Babjuk M, Bohle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71(3):447–61.4. Gaul Frau J, Palou J, Rodriguez O, et al. Failure of Bacillus Calmette-Guerin therapy innon-muscle-invasive bladder cancer: definition and treatment options. Arch Esp Urol. 2016;69(7):423–33.5. Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466-477.6. Ritch CR, Velasquez MC, Kwon D, et al. Use and Validation of the AUA/SUO Risk Grouping for Nonmuscle Invasive Bladder Cancer in a Contemporary Cohort. J Urol. 2020;203(3):505-511.                                                                                            往期 · 推荐遏制耐药，拯救生命，我们在行动！生命的韧性：与多发性骨髓瘤共处辉瑞靶向免疫疗法易瑞欧®（埃纳妥单抗）在华获批，用于治疗复发或难治性多发性骨髓瘤【一键通达】药品问询不再难，医学信息解忧烦!

iStock, Sundry Photography The news comes on the heels of promising Phase I/Ib data, which point to the potential of casdatifan as a more effective alternative to Merck’s Welireg in renal cell carcinoma. Gilead will not move forward with Arcus Biosciences’ casdatifan, an investigational HIF-2a blocker that is being tested for kidney cancer. As per the California biotech’s Tuesday press announcement, Gilead’s window to exercise its exclusive option to obtain rights to casdatifan has “expired.” Arcus will retain full control over the asset and its development path forward. Arcus also announced that it will run a $150 million common stock offering—which Gilead will participate in—to help bankroll future studies of casdatifan. Arcus CEO Terry Rosen in a statement said that the biotech is “thrilled” to keep ownership of casdatifan, which he says “represents a transformational change for Arcus” and allows it to “address a significant unmet need for patients with an estimated $5 billion market opportunity.” Investors, however, are not as enthused: Arcus’ shares dipped 16% to $10.96 on Tuesday, a new 52-week low for the company, per SeekingAlpha . Analysts at Mizuho Securities, on the other hand, appeared optimistic about Arcus, writing in a Tuesday note that the stock offering “could allow [Arcus] to advance the casdatifan program independently” and provide freedom to assess the candidate as a monotherapy or as part of combination regimens. Tuesday’s news comes just days after Arcus presented promising Phase I/Ib data for casdatifan at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Results, disclosed over the weekend, showed that a 100-mg dose, given once a day, resulted in a 33% confirmed overall response rate (ORR) and a 52% stable disease rate in patients with metastatic clear cell renal cell carcinoma (RCC). Patients treated with this casdatifan dosage did not reach median progression-free survival (PFS) at the time of the readout, though a different dose level—50 mg twice-daily—had a median PFS of 9.7 months. Arcus is taking the 100-mg dose forward. According to Mizuho, these data suggest that casdatifan is “superior” to Merck’s Welireg (belzutifan), which is also a HIF-2a inhibitor that is FDA-approved for advanced RCC. In particular, the analysts zeroed in on casdatifan’s 9.7-month PFS in the 50-mg, once-daily dose arm, which they say compares favorably to Welireg’s 5.6-month PFS, as indicated in its label . Additionally, casdatifan’s 33% ORR is higher than Welireg’s 22%, as per Mizuho. Cross-study comparisons are inconclusive, however, in the absence of direct head-to-head trials. Arcus plans to ramp up investment to “position casdatifan as the HIF-2a inhibitor of choice,” Rosen said in a statement. The biotech will unveil more data for the therapy throughout 2025 and is preparing to launch another study, dubbed PEAK-1, which will test casdatifan with Cabometyx , Exelixis’s VEGF2 inhibitor, in metastatic clear cell RCC patients who had previously undergone immune-oncology treatments.

Pfizer has shared promising top-line results from a phase 3 study of sasanlimab as an induction therapy in a subset of bladder cancer patients. The phase 3 CREST trial has been evaluating the subcutaneously-administered investigational anti-PD-1 monoclonal antibody in combination with standard-of-care Bacillus Calmette-Guérin (BCG), with or without maintenance, in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). Approximately 10,500 people are diagnosed with bladder cancer in the UK every year and NMIBC, in which the cancer cells are confined to the inner lining of the bladder, accounts the majority of new cases. Despite induction therapy with BCG followed by maintenance, up to 50% of high-risk NMIBC patients experience disease recurrence and often require a radical cystectomy, which is associated with significant risks. CREST met its primary endpoint, with sasanlimab plus BCG demonstrating a clinically meaningful and statistically significant improvement in event-free survival compared to BCG alone. The overall safety profile of the combination was also shown to be generally consistent with the known profile of BCG and with data reported from clinical trials of sasanlimab, Pfizer said. “The initial therapy of high-risk, NMIBC with BCG has not advanced in decades,” said Roger Dansey, chief oncology officer at Pfizer. “[These] pivotal phase 3 CREST results are potentially practice-changing, representing the first advance in therapy for BCG-naïve, high-risk, non-muscle invasive cancer in over 30 years.” Pfizer said it is planning to discuss the results with global health authorities to support potential regulatory filings for sasanlimab in this indication, adding that it will continue to evaluate the drug in combination with its antibody drug conjugate portfolio in advanced solid tumours. The announcement comes three months after Pfizer and its Astellas-partnered Padcev (enfortumab vedotin) was approved by the Medicines and Healthcare products Regulatory Agency in combination with Merck & Co’s – known as MSD outside the US and Canada – Keytruda (pembrolizumab) to treat advanced bladder cancer. The antibody-drug conjugate/PD-1 inhibitor combination was specifically authorised by the UK regulator to treat unresectable or metastatic urothelial carcinoma in adults who are eligible for platinum-containing chemotherapy.