Core Viewpoint - The FRUSICA-2 study results indicate that the combination of fruquintinib and sintilimab may provide a valuable new treatment option for patients with advanced renal cell carcinoma, addressing significant unmet medical needs in this patient population [1][3]. Group 1: Study Overview - The FRUSICA-2 study is a randomized, open-label, positive-controlled registration trial aimed at evaluating the efficacy and safety of fruquintinib combined with sintilimab compared to axitinib or everolimus monotherapy for second-line treatment of advanced renal cell carcinoma [1]. - A total of 234 patients were randomly assigned to receive either the combination therapy or monotherapy [1]. Group 2: Efficacy Results - The median progression-free survival (PFS) for the fruquintinib and sintilimab group was 22.2 months, compared to 6.9 months for the axitinib/everolimus group, with a stratified hazard ratio (HR) of 0.373 and a p-value of <0.0001 [2]. - The objective response rate (ORR) was 60.5% for the combination therapy versus 24.3% for the monotherapy, with an odds ratio of 4.622 and a p-value of <0.0001 [2]. - The median duration of response (DoR) was 23.7 months for the combination group compared to 11.3 months for the monotherapy group [2]. Group 3: Safety Profile - The combination therapy demonstrated a tolerable safety profile, consistent with known characteristics of the treatments, with 71.4% of patients experiencing grade 3 or higher treatment-emergent adverse events (TEAEs) compared to 58.8% in the axitinib/everolimus group [2]. Group 4: Regulatory Progress - Based on the FRUSICA-2 study data, the National Medical Products Administration of China has accepted the new drug application for the combination therapy for patients with locally advanced or metastatic renal cell carcinoma who have previously failed systemic treatment [3].

FRUSICA-2研究的联合主要研究者、北京大学第一医院何志嵩教授表示："FRUSICA-2研究表明，呋喹 替尼和信迪利单抗的联合疗法有望为晚期肾细胞癌的二綫治疗策略带来变革。该联合疗法展现出改善临 床结局的潜力，为应对这一具有挑战性的疾病提供了新的治疗选择。" 基于FRUSICA-2研究的数据，中国国家药品监督管理局(国家药监局)已受理呋喹替尼和信迪利单抗的联 合疗法用于既往接受过系统治疗失败的局部晚期或转移性的肾细胞癌患者的新药上市申请。 呋喹替尼联合信迪利单抗的盲态独立中心阅片(BICR)评估的中位PFS为22.2个月，阿昔替尼/依维莫司组 则为6.9个月(分层风险比[HR]0.373;分层log-rank检验p<0.0001)。客观缓解率(ORR)分别为60.5%对比 24.3%(优势比4.622，p<0.0001)，中位缓解持续时间(DoR)分别为23.7个月对比11.3个月。截至数据截止 时，总存活期数据仍在持续积累中，成熟度约为20%。在根据国际转移性肾细胞癌数据库联盟(IMDC) 标准划分的所有预后风险组中，均观察到疗效获益。 呋喹替尼和信迪利单抗的联合疗法展示出可耐受的安全性，并与各项治疗的 ...

格隆汇10月13日丨和黄医药(00013.HK)今日公布呋喹替尼(fruquintinib)联合信迪利单抗(sintilimab)用于治 疗局部晚期或转移性肾细胞癌患者的FRUSICA-2注册研究结果。该研究III期部分的结果将于2025年10 月17日(星期五)在德国柏林举行的欧洲肿瘤内科学会( "ESMO")年会上公布。 FRUSICA-2是一项随机、开放标签、阳性对照的注册研究，旨在评估呋喹替尼和信迪利单抗联合疗法 对比阿昔替尼(axitinib)或依维莫司(everolimus)单药疗法用于二线治疗晚期肾细胞癌的疗效和安全性 (NCT05522231)。共234位患者被随机分配至呋喹替尼和信迪利单抗联合疗法治疗组，或阿昔替尼或依 维莫司单药疗法治疗组。至无进展生存期("PFS")最终分析截止日2025年2月17日，中位随访时间为16.6 个月。 喹替尼联合信迪利单抗的盲态独立中心阅片(BICR)评估的中位PFS为22.2个月 ，阿昔替尼/依维莫司组则 为6.9个月(分层风险比 [HR] 0.373 ；分层log-rank检验 p <0.0001) 。客观缓解率(ORR)分别为60.5%对比 24.3% ...

Core Viewpoint - The article discusses the case of a patient diagnosed with Birt-Hogg-Dubé (BHD) syndrome, highlighting the rapid recurrence of kidney cancer post-surgery and the importance of genetic testing for accurate diagnosis and management [1][2]. Group 1: BHD Syndrome Overview - BHD syndrome is an autosomal dominant genetic disorder caused by mutations in the FLCN gene, with a 50% inheritance probability from an affected parent [2]. - The estimated prevalence of BHD syndrome is approximately 1-2 per million, but actual numbers may be higher due to underdiagnosis of mild or asymptomatic cases [2]. Group 2: Clinical Manifestations - Skin manifestations include small, painless, skin-colored or light red papules on the face, often misdiagnosed as acne or age spots [3]. - Lung involvement is characterized by thin-walled cysts that can lead to spontaneous pneumothorax, commonly misdiagnosed in young, tall individuals [4]. - About one-third of BHD patients will develop kidney tumors, typically presenting bilaterally and multifocally, with an average onset age of 50 [5]. Group 3: Sarcomatoid Change - Sarcomatoid change is not a new cancer but a transformation of existing renal cancer, marked by rapid growth and increased aggressiveness [6]. - The occurrence of sarcomatoid change in the context of BHD syndrome is rare but significantly impacts clinical outcomes, leading to increased invasiveness and reduced survival [6]. Group 4: Treatment Adjustments - The initial treatment with axitinib and PD-1 inhibitors failed within six weeks, indicating a more aggressive tumor behavior [7]. - A multidisciplinary team (MDT) decided to switch to an alternative treatment regimen involving anlotinib combined with immunotherapy [8]. - After four months, the tumor size decreased from 12 cm to 5 cm, indicating a partial response to the new treatment plan [9]. Group 5: Diagnosis and Management of BHD - Early suspicion of BHD should arise in cases of early-onset or bilateral/multifocal kidney tumors, or when associated with spontaneous pneumothorax [10]. - Genetic testing for FLCN mutations can be performed through blood or saliva samples, with results available in about two weeks [11]. - Management strategies include annual MRI scans of the kidneys starting at age 20, regular chest CT scans, and monitoring skin lesions [12].

Investment Rating - The report does not explicitly state an investment rating for the pharmaceutical and biotechnology industry, but it indicates a positive outlook on the innovation drug sector, particularly regarding the international expansion of domestic innovative drugs [3][4]. Core Insights - The report highlights the continuous rise in the enthusiasm for innovative drugs going overseas, with significant collaborations such as the $9 billion partnership between Bristol-Myers Squibb and BioNTech for the development of a PD-L1/VEGF dual antibody [3][4]. - It notes that the domestic innovative drug pipeline is becoming increasingly competitive on a global scale, with a long-term positive outlook for the internationalization of innovative drugs [3][4]. - The report also discusses the recent peak of COVID-19 cases in China, with a positivity rate of 23.8% reported at the end of May, indicating a need for continued monitoring [3][4]. Market Weekly Review - The pharmaceutical and biotechnology sector rose by 1.13% from June 3 to June 6, underperforming compared to the Wind All A index, which increased by 1.61% [9][10]. - Among sub-sectors, raw materials and blood products both saw a rise of 2.89%, while in vitro diagnostics increased by 2% [10]. - Notable stock performances included Yiming Pharmaceutical with a 33.1% increase, while *ST Longjin experienced a significant decline of 36.3% [12]. Industry News and Key Company Announcements - Significant events include the presentation of clinical data for IBI363 by Innovent Biologics at the ASCO conference, showing promising efficacy in treating advanced non-small cell lung cancer [12][13]. - Stone Pharmaceutical received approval for its adenosylcobalamin capsules, expanding its product line in the blood and nervous system treatment areas [13]. - CanSino Biologics announced the approval of a new indication for its PD-1/CTLA-4 inhibitor, filling a gap in the treatment of cervical cancer in China [13]. - The report also mentions various other approvals and collaborations among companies, indicating a vibrant and active industry landscape [13][14].

Investment Rating - The report does not explicitly state an investment rating for the pharmaceutical and biotechnology industry, but it indicates a positive outlook on the global competitiveness of domestic innovative drugs and the trend of innovative drugs going abroad [3][4]. Core Viewpoints - The innovative drug sector is experiencing a surge in overseas collaboration, highlighted by the partnership between Bristol-Myers Squibb and BioNTech to jointly develop a PD-L1/VEGF dual antibody with a total package worth $9 billion [3][4]. - The report notes that the recent ASCO conference showcased significant advancements in dual antibodies and ADCs, indicating a differentiated layout in early clinical stages for domestic innovative drugs [3][4]. - The report mentions a peak in the current COVID-19 wave, with a positivity rate of 23.8% reported at the end of May, which is higher than the entire year of 2024, although it has started to decline slightly [3][4]. Weekly Market Review - The pharmaceutical and biotechnology sector rose by 1.13% from June 3 to June 6, underperforming the Wind All A index, which increased by 1.61% [9][10]. - Among sub-sectors, raw materials and blood products both increased by 2.89%, while in vitro diagnostics rose by 2% [9][10]. - Notable stock performances included Yiming Pharmaceutical with a rise of 33.1%, Wanbangde at 32.6%, and Anglikang at 30.3%, while *ST Longjin fell by 36.3%, Huason Pharmaceutical by 12.4%, and Maipu Medical by 9.3% [12][10]. Industry News and Key Company Announcements - On June 4, Innovent Biologics reported promising Phase I clinical data for IBI363 in treating advanced non-small cell lung cancer at the ASCO annual meeting [12][13]. - On June 6, CSPC announced that its adenosylcobalamin capsules received drug registration approval from the National Medical Products Administration [13][14]. - On June 5, CanSino Biologics announced the approval of a new indication for its PD-1/CTLA-4 inhibitor in first-line treatment for cervical cancer [13][14]. - On June 2, Bristol-Myers Squibb and BioNTech announced a collaboration to develop the PD-L1/VEGF dual antibody BNT327, with a significant financial commitment involved [13][14].