A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

开始日期2018-03-23

申办/合作机构

Janssen Research & Development LLC

NCT02845050

/ Withdrawn临床1/2期

Phase Ib/II Study Assessing the Neo-adjuvant Combination Therapy of Vinflunine With Cisplatin Followed by Radical Cystectomy in Patients With Muscle-invasive Bladder Cancer (JaNEO)

Phase Ib/II study assessing the neo-adjuvant combination therapy of vinflunine with cisplatin followed by radical cystectomy in patients with muscle-invasive bladder cancer (JaNEO).

开始日期2016-07-01

申办/合作机构

Ligartis SA

EUCTR2014-005396-82-AT

/ Not yet recruiting临床3期

Randomized phase III study comparing vinflunine-gemcitabine and gemcitabine-carboplatin combinations in patients ineligible to cisplatin with advanced or metastatic urothelial carcinoma. - Jasint-2

开始日期2016-01-29

申办/合作机构

Pierre Fabre Medicament Information

100 项与酒石酸长春氟宁相关的临床结果

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100 项与酒石酸长春氟宁相关的转化医学

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100 项与酒石酸长春氟宁相关的专利（医药）

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项与酒石酸长春氟宁相关的文献（医药）

2025-11-01·EUROPEAN UROLOGY

Impact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial

Article

作者: Sternberg, Cora N. ; Quinn, David I ; Xu, Jin ; Sternberg, Cora N ; Culine, Stéphane ; Petrylak, Daniel P. ; Choueiri, Toni K. ; Vaughn, David J. ; Homet Moreno, Blanca ; Choueiri, Toni K ; Climent, Miguel A. ; Petrylak, Daniel P ; Quinn, David I. ; Gerritsen, Winald R. ; Gurney, Howard ; Fong, Lawrence ; de Wit, Ronald ; Climent, Miguel A ; Fradet, Yves ; Imai, Kentaro ; Gerritsen, Winald R ; Lee, Jae-Lyun ; Bajorin, Dean F ; Vaughn, David J ; Necchi, Andrea ; Bellmunt, Joaquim ; Bajorin, Dean F.

BACKGROUND AND OBJECTIVE:

Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.

METHODS:

Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m²], docetaxel [75 mg/m²], or vinflunine [320 mg/m²], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response.

KEY FINDINGS AND LIMITATIONS:

An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing.

CONCLUSIONS AND CLINICAL IMPLICATIONS:

When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC.

2025-08-01·Clinical Genitourinary Cancer

Erdafitinib versus Chemotherapy in Fibroblast Growth Factor Receptor-Altered Advanced or Metastatic Urothelial Cancer After Progression on Anti-programmed Death-(Ligand) 1 Therapy: An Exploratory Analysis of the Asian Subpopulation in the THOR Phase 3 Study

Article

作者: Siefker-Radtke, Arlene O ; Xue, Wei ; Xing, Nianzeng ; Tran, Ben ; Hemaya, Rosemary ; Zhuo, Jianmin ; Loriot, Yohann ; Huang, Jian ; Ku, Ja Hyeon ; Huang, Yi-Hsiu ; Burgess, Earle F ; Park, Se Hoon ; Nishimura, Kazuo ; Triantos, Spyros ; Deprince, Kris ; Huddart, Robert A ; Matsubara, Nobuaki ; Shimizu, Nobuaki

INTRODUCTION:

The randomized phase 3 THOR study showed significantly longer survival with erdafitinib (pan-fibroblast growth factor receptor [FGFR] inhibitor) over chemotherapy in adults with FGFR-altered locally advanced or metastatic urothelial cancer (la/mUC) who had progressed during or after anti-programmed death-(ligand) 1 (anti-PD-[L]1) therapy (Cohort 1). This exploratory post-hoc analysis was conducted to evaluate the efficacy and safety of erdafitinib in the Asian subpopulation within THOR Cohort 1.

PATIENTS AND METHODS:

Eligible patients were randomized in a 1:1 ratio to receive erdafitinib (8 mg once daily with pharmacodynamically guided up-titration to 9 mg) or chemotherapy (vinflunine or docetaxel once every 3 weeks). The primary endpoint was overall survival (OS).

RESULTS:

Seventy-six patients were included in the Asian subpopulation: 37 were randomized to erdafitinib and 39 to docetaxel. The median follow-up for survival was 15.7 months. The median OS was longer with erdafitinib than chemotherapy (23.3 months vs.11.3 months; hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.23-0.96). One patient (2.7%) in the erdafitinib arm and 5 patients (15.2%) in the chemotherapy arm had grade 3 or 4 treatment-related serious adverse events (SAEs). One patient (2.7%) in the erdafitinib arm and 4 patients (12.1%) in the chemotherapy arm discontinued treatment due to treatment-related AEs.

CONCLUSIONS:

Erdafitinib showed improved survival compared with chemotherapy, with no new safety concerns in the Asian subpopulation. These findings were consistent with those for the overall study population in THOR Cohort 1 who received prior anti-PD-(L)1 therapy.

2025-05-01·ANNALS OF ONCOLOGY

Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial

Article

作者: Waldes, J ; Sierecki, M ; Grivas, P ; Kovalenko, M ; Guo, J ; Morales-Barrera, R ; Sternberg, C N ; Necchi, A ; Vulsteke, C ; Boateng, F ; Duran, I ; Loriot, Y ; Gross-Goupil, M ; Park, S H ; Sima, C S ; Goebell, P J ; De Santis, M ; Wang, L ; Bellmunt, J ; Tagawa, S ; Powles, T

BACKGROUND:

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, demonstrated efficacy and manageable toxicity in the phase II TROPHY-U-01 study in pretreated advanced urothelial carcinoma (aUC). We report the results from final analysis of the global open-label randomized phase III TROPiCS-04 study (NCT04527991) in pretreated aUC.

PATIENTS AND METHODS:

Patients with aUC whose disease had progressed on prior platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1 : 1 to receive SG or treatment of physician's choice (TPC; paclitaxel, docetaxel, or vinflunine). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by investigator and blinded independent committee review, as well as safety.

RESULTS:

Overall, 711 patients were randomized. After a median follow-up of 9.2 months, the primary endpoint was not met [median OS for SG versus TPC: 10.3 months versus 9.0 months, hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.02, P = 0.087]. Median PFS with SG and TPC was 4.2 months and 3.6 months, respectively (HR 0.86, 95% CI 0.72-1.03); ORR (95% CI) was 23% (18% to 27%) and 14% (10% to 18%). The most common grade ≥3 treatment-related adverse event (TRAE) with SG was neutropenia (35%, including 12% with febrile neutropenia). Incidence of grade ≥3 TRAEs (67% versus 35%) and grade 5 treatment-emergent adverse events (TEAEs; 7% versus 2%) was higher with SG versus TPC. In the SG group, 16/25 grade 5 TEAEs were infections with neutropenia mostly occurring early in the treatment course of patients with multiple risk factors for febrile neutropenia. Primary prophylactic granulocyte colony-stimulating factor (G-CSF) usage with SG and TPC was 21% and 22%, respectively.

CONCLUSIONS:

SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR. Early toxicity-related complications with SG may have impacted efficacy outcomes.

项与酒石酸长春氟宁相关的新闻（医药）

2025-03-06

·精准药物

2025年1-2月国内外抗肿瘤药物获批情况一览

据公开资料显示，2025年1-2月共有FDA批准新适应症4条，NMPA批准新适应症12条。靶向药物新获批主要针对EGFR、ROS1、MET、KRAS、BRCA1/2、FGFR3等靶点基因。详细1-2月获批上市药物及药物新获批适应症见下文。 1 Part.1 新药速递（概括版） 2 Part.2 新药速递（详细版） 1. 奥希替尼/ 商品名：泰瑞沙通用名：奥希替尼适应症：接受含铂放化疗期间或之后未出现疾病进展、具有EGFR 19del或L858R突变的III期NSCLC 临床试验：LAURA 原研公司：阿斯利康获批日期：2025.01.02 获批机构：NMPA 2025年1月2日，NMPA批准奥希替尼用于接受含铂放化疗期间或之后未出现疾病进展、具有EGFR 19del或L858R突变的局部晚期、不可切除（III期）NSCLC成人患者的治疗。此前，2024年9月25日，FDA批准奥希替尼用于接受同步或序贯铂类放化疗期间或之后且无疾病进展、携带敏感突变（EGFR 19del或L858R突变）的局部晚期、不可切除（III期）NSCLC成人患者的治疗。截至目前，奥希替尼在NSCLC患者中的获批适应症，从晚期扩展到早期，从后线治疗走向前线治疗，从单药治疗到联合治疗，再到根治性放化疗后的巩固治疗。本次获批是基于一项双盲、随机、安慰剂对照的III期临床试验LAURA（NCT03521154），该研究旨在比较奥希替尼与安慰剂在携带EGFR敏感突变的局部晚期、不可切除的III期NSCLC患者（这些患者在根治性同步/序贯放化疗后且无疾病进展）的疗效。研究主要终点是BICR评估的无进展生存期（PFS），次要终点包括总生存期（OS）、中枢神经系统（CNS）PFS、安全性等。结果显示，共计来自美国、欧洲、南美和亚洲地区超过15个国家、145+中心的216例接受过根治性放化疗后疾病未进展的患者被随机分配接受奥希替尼（143人）或安慰剂（73人）巩固治疗。与安慰剂相比，奥希替尼带来显著的中位PFS获益（39.1个月 vs. 5.6个月）；奥希替尼组和安慰剂组的1年的PFS率分别为74%和22%，2年PFS率分别为65%和13%。在CNS控制方面：奥希替尼组的CNS PFS较安慰剂组降低了83%的颅内疾病进展或死亡风险（HR=0.17，95%CI：0.009-0.32），两组的中位CNS PFS分别为NR和14.9个月；此外，奥希替尼治疗组新发脑转移病灶的发生率（8% vs. 29%）和CNS进展的累积发生率（9% vs. 36%）也更低。2024 ESMO大会上首次公布了LAURA研究中国亚组的临床数据。结果显示，中国队列的临床数据与全球人群一致，相较安慰剂组，奥希替尼组保持着明显的PFS获益趋势（1年PFS率：80% vs. 17%；2年PFS率：71% vs. 8%）。 LAURA研究中国队列数据 2. 奥拉帕利/ 商品名：利普卓通用名：奥拉帕利适应症：携带有害或疑似有害胚系BRCA突变（gBRCAm）、HER2阴性早期高风险乳腺癌的辅助治疗临床试验：OlympiA 原研公司：阿斯利康、默沙东获批日期：2025.01.02 获批机构：NMPA 2025年1月2日，NMPA批准奥拉帕利用于接受过新辅助或辅助化疗的携带有害或疑似有害胚系BRCA突变（gBRCAm）、HER2阴性早期高风险乳腺癌成人患者的辅助治疗。截至目前为止，这是在中国大陆首个且唯一获批针对早期乳腺癌BRCA突变的靶向治疗药物。本次获批是基于一项双盲、安慰剂对照、多中心的III期临床试验OlympiA，该研究旨在比较奥拉帕利片剂与安慰剂作为辅助治疗在胚系BRCA突变、HER2阴性早期高风险乳腺癌患者的疗效和安全性，且这些患者都已完成根治性局部治疗和新辅助或辅助化疗。结果显示，奥拉帕利组3年无浸润性疾病生存期（iDFS）率显著优于安慰剂组（85.9% vs. 77.1%），患者的疾病复发、新发癌症或死亡风险降低了42%（HR=0.58，P<0.001）。奥拉帕利组实现无远端转移疾病生存期（dDFS）达到3年的患者比例同样更高（87.5% vs. 80.4%），远端转移风险降低了43%（HR=0.57，P<0.001）。此外，对比安慰剂组，奥拉帕利组实现总生存期（OS）达到3年的患者比例也更高（92.0% vs. 88.3%），死亡风险降低了32%（HR=0.68，P=0.02）。 OlympiA研究数据 3. 他雷替尼/ 商品名：达伯乐通用名：他雷替尼适应症：未经ROS1-TKI治疗的ROS1阳性局部晚期或转移性NSCLC 临床试验：TRUST-I 原研公司：第一三共获批日期：2025.01.02 获批机构：NMPA 2025年1月2日，NMPA批准他雷替尼用于未经ROS1-TKI治疗的ROS1阳性局部晚期或转移性NSCLC成人患者的一线治疗。2024年12月20日，NMPA批准他雷替尼用于治疗经ROS1-TKI治疗失败的ROS1阳性局部晚期或转移性NSCLC成人患者。ROS1-TKI作为ROS1阳性晚期NSCLC标准治疗选择，为该类患者带来了生存获益改善并在临床中得以广泛应用，但仍面临脑转移控制不佳、颅内活性及其伴随风险难以平衡、靶向治疗耐药等重大挑战。他雷替尼作为新一代强效、高脑渗透、高选择性的ROS1-TKI，展现出突破ROS1阳性NSCLC治疗困境的潜力，本次新适应症的获批让其成为ROS1阳性晚期NSCLC全线治疗新选择。本次获批是基于一项在中国开展的多中心、开放标签、单臂的II期临床试验TRUST-I（NCT04395677），研究纳入173名ROS1阳性晚期NSCLC患者并接受他雷替尼治疗，其中初治患者106名，既往接受克唑替尼治疗后耐药的患者67名。该研究的主要终点是独立审查委员会（IRC）根据RECIST v1.1评估经确认的客观缓解率（ORR），次要终点则包括缓解持续时间（DOR）、无进展生存期（PFS）等。结果显示，在106名未接受TKI治疗的患者中，IRC评估经确认的ORR达90.6%（95%CI，83.33-95.38），其中4例患者达完全缓解（CR），92例（86.8%）患者达部分缓解（PR），疾病控制率（DCR）为95.3%（95%CI，89.33-98.45）。此外，患者24个月的DOR和PFS率分别为78.6%（95%CI，66.86-86.56）和70.5%（95%CI，59.17-79.16）。 TRUST-I研究数据 4. 帕博利珠单抗/ 商品名：可瑞达通用名：帕博利珠单抗适应症：联合注射用维恩妥尤单抗用于一线治疗局部晚期或转移性尿路上皮癌临床试验：EV-302（KEYNOTE-A39）原研公司：默沙东获批日期：2025.01.08 获批机构：NMPA 2025年1月8日，NMPA批准帕博利珠单抗联合注射用维恩妥尤单抗用于既往未经治疗的局部晚期或转移性尿路上皮癌（UC）成人患者的一线治疗。维恩妥尤单抗是全球首个获批靶向Nectin-4的抗体偶联药物（ADC），无需生物标志物检测。此次，帕博利珠单抗联合注射用维恩妥尤单抗的新适应症获批，将为更多尿路上皮癌患者带来新的选择。本次获批是基于一项开放标签、随机对照、全球性的III期临床试验EV-302（KEYNOTE-A39，NCT04223856），旨在评估帕博利珠单抗+维恩妥尤单抗对比化疗治疗既往未经治疗的局部晚期或转移性UC患者的疗效和安全性。研究纳入了886名既往未经治疗的局部晚期或转移性UC且能耐受含铂化疗的患者，无论其PD-L1表达状态，随机1：1分配到帕博利珠单抗+维恩妥尤单抗治疗组（P+EV，n=442）和化疗组（吉西他滨联合顺铂/卡铂，n=444）。结果显示，截至2023年8月8日，中位随访时间17.2个月，P+EV治疗组的中位总生存期（OS）较化疗组延长了15.4个月（31.5个月 vs. 16.1个月），死亡风险降低了53%（HR=0.47；95%CI：0.38-0.58；P<0.00001）；对比化疗组，P+EV治疗组提高了患者的中位无进展生存期（PFS）（12.5个月 vs. 6.2个月）；无论患者能否接受顺铂治疗，都能观察到OS和PFS获益，并且不受PD-L1状态或有无内脏转移的影响。此外，P+EV治疗组患者的客观缓解率（ORR）高于化疗组（67.7% vs. 44.4%），P+EV治疗组达到完全缓解（CR）的患者高达29.1%，而化疗组仅为12.5%。 EV-302研究数据 5. 帕博利珠单抗/ 商品名：可瑞达通用名：帕博利珠单抗适应症：PD-L1（CPS≥1）的转移性或不可切除的复发性头颈部鳞癌临床试验：KEYNOTE-048 原研公司：默沙东获批日期：2025.01.13 获批机构：NMPA 2025年1月13日，NMPA批准帕博利珠单抗用于肿瘤细胞表达PD-L1（CPS≥1）的转移性或不可切除的复发性头颈部鳞癌（HNSCC）患者的一线治疗。2020年12月，NMPA批准帕博利珠单抗单药用于PD-L1（CPS≥20）的转移性或不可切除的复发性头颈部鳞状细胞癌患者的一线治疗。此次适应症的扩展降低了对于患者PD-L1表达情况的要求，从原来的CPS≥20降至CPS≥1，有望让更多HNSCC患者受益于创新治疗方案。本次获批是基于一项随机、开放标签、多中心III期临床试验KEYNOTE-048，该研究旨在比较帕博利珠单抗单药、帕博利珠单抗联合化疗（顺铂/卡铂+5-氟尿嘧啶）与EXTREME方案（西妥昔单抗+顺铂/卡铂+5-氟尿嘧啶）的有效性和安全性。主要终点包含总生存期（OS）与无进展生存期（PFS）。结果显示，在随访5年时间后，在PD-L1 CSP≥1的转移性或不可切除的复发性HNSCC人群中，帕博利珠单抗单药组的中位OS为12.3个月，EXTREME组的中位OS为10.4个月，5年OS率分别为15.4%和5.5%。帕博利珠单抗联合化疗组与EXTREME组相比，中位OS分别为13.6个月和10.6个月，5年OS率分别为18.2%和4.3%。 KEYNOTE-048研究数据 6. 赛沃替尼/ 商品名：沃瑞沙通用名：赛沃替尼适应症：MET基因外显子14跳读突变的初治局部晚期或转移性NSCLC 临床试验：NCT04923945 原研公司：和黄医药获批日期：2025.01.13 获批机构：NMPA 2025年1月13日，NMPA批准赛沃替尼用于MET基因外显子14跳读突变的局部晚期或转移性NSCLC成人患者的一线治疗。2021年6月，NMPA附条件批准赛沃替尼用于治疗接受系统治疗后疾病进展或无法接受化疗的MET基因外显子14跳读突变的NSCLC患者，目前已转为常规批准。本次获批，意味着赛沃替尼在国内MET基因外显子14跳读突变的NSCLC领域全面覆盖初治和经治患者。本次获批基于一项单臂、多队列、多中心、开放标签的IIIb期临床试验NCT04923945，该研究在中国48家医院进行，纳入125名既往未接受过全身抗肿瘤治疗的携带MET基因外显子14跳读突变的局部晚期或转移性NSCLC成人患者，最终有87例患者接受赛沃替尼治疗。该研究旨在评估赛沃替尼在MET基因外显子14跳读突变的局部晚期或转移性NSCLC成人患者中的疗效和安全性，主要终点是独立审查委员会（IRC）根据RECIST v1.1版评估的客观缓解率（ORR），次要终点为研究者评估的ORR，IRC评估和研究者评估的疾病控制率（DCR）和缓解持续时间（DOR）等。结果显示，接受赛沃替尼治疗的初治患者中，IRC评估的ORR为62%，研究者评估的ORR为60%；两者评估患者的DCR都达到92.0%，中位DOR都为12.5个月。其次，至中位随访时间20.8个月时，IRC评估患者中位无进展生存期（PFS）为13.7个月。 NCT04923945研究数据 7. 厄达替尼/ 商品名：博珂通用名：厄达替尼适应症：携带FGFR3基因变异，且既往接受至少一线含抗PD-1或抗PD-L1治疗的尿路上皮癌临床试验：THOR 原研公司：强生获批日期：2025.01.13 获批机构：NMPA 2025年1月13日，NMPA批准厄达替尼用于治疗携带FGFR3基因变异，且既往接受至少一线含抗PD-1或抗PD-L1期间或之后出现疾病进展的手术不可切除的局部晚期或转移性尿路上皮癌（UC）成人患者。2024年1月，FDA批准厄达替尼用于既往接受至少一种全身治疗后出现疾病进展的携带FGFR3基因变异的局部晚期或转移性尿路上皮癌（UC）的成人患者的治疗。本次获批是基于一项全球III期临床试验THOR（NCT03390504），该研究共入组266例转移性或手术无法切除的UC患者，且在接受过一至两次包括抗PD-1或抗PD-L1在内的治疗后病情出现进展，以上患者按1∶1随机分配到厄达替尼治疗组（136例）和化疗组（130例，多西他赛或长春氟宁），中位随访时间为15.9个月。经检测，266例患者中有215例存在FGFR变异（突变或融合：没有患者携带FGFR2变异，46.6%携带FGFR3 S249C突变，16.9%携带FGFR3 Y373C突变，9.8%携带FGFR3–TACC3_V1融合）。结果显示，厄达替尼组的客观缓解率（ORR）明显高于化疗组（45.6% vs. 11.5%）；厄达替尼组有9例患者（6.6%）达到完全缓解（CR），53例（39.0%）患者达到部分缓解（PR），化疗组有1例患者（0.8%）达到CR，14例患者（10.8%）达到PR；此外，厄达替尼组的中位无进展生存期（PFS）长于化疗组（5.6个月 vs. 2.7个月），厄达替尼组的中位总生存期（OS）也显著优于化疗组（12.1个月 vs. 7.8个月）。 THOR研究数据 8. 利厄替尼/ 商品名：奥壹新通用名：利厄替尼适应症：既往接受EGFR-TKI治疗出现疾病进展且EGFR T790M阳性的局部晚期或转移性NSCLC 临床试验：NCT03502850 原研公司：信达生物、奥赛康药业获批日期：2025.01.16 获批机构：NMPA 2025年1月16日，NMPA批准利厄替尼用于既往接受EGFR-TKI治疗时或治疗后出现疾病进展，并且经检测确认存在EGFR T790M突变阳性的局部晚期或转移性NSCLC成人患者的治疗。利厄替尼由奥赛康药业与上海药物所、广州健康院合作开发，是一款高选择性、不可逆第三代EGFR-TKI。在利厄替尼获批前，国内正式获批EGFR T790M阳性的EGFR-TKI已有六款，分别是奥希替尼、阿美替尼、伏美替尼、贝福替尼、瑞齐替尼和瑞厄替尼。本次获批基于一项单臂、开放标签的IIb期临床试验NCT03502850，研究旨在评估利厄替尼在既往EGFR-TKI治疗后进展的T790M阳性局部晚期或转移性NSCLC患者中的疗效与安全性。研究共纳入了301例经既往EGFR-TKI治疗后进展的EGFR T790M突变阳性或原发性EGFR T790M突变阳性的局部晚期或转移性NSCLC患者。结果显示，经独立评审委员会（IRC）评估的客观缓解率（ORR）为68.8%，疾病控制率（DCR）为92.4%，缓解持续时间（DOR）为11.1个月，无进展生存期（PFS）为11.0个月，总生存期（OS）数据尚未成熟。CNS患者颅内ORR为56.1%，PFS为10.6个月，提示利厄替尼对CNS患者具有较好的疗效。 NCT03502850研究数据 9. 塞纳帕利/ 商品名：派舒宁通用名：塞纳帕利适应症：FIGO分期III-IV期的上皮性卵巢癌、输卵管癌或原发性腹膜癌的维持治疗临床试验：FLAMES 原研公司：英派药业获批日期：2025.01.16 获批机构：NMPA 2025年1月16日，NMPA批准塞纳帕利用于国际妇产科联盟（“FIGO”）III-IV期上皮性卵巢癌、输卵管癌或原发性腹膜癌患者在一线含铂化疗达到完全或部分缓解后的维持治疗。塞纳帕利是由英派药业自主研发的新型、高效的PARP1/2抑制剂，其独特的分子结构确保了出色的靶向选择性和广泛的安全窗口。本次获批基于一项随机、双盲、安慰剂对照、多中心的III期临床试验FLAMES（NCT04169997/CTR20192330），该研究旨在评价一线含铂化疗达到完全缓解（CR）或部分缓解（PR）后塞纳帕利单药维持治疗FIGO III-IV期卵巢癌患者的有效性和安全性。研究纳入404例新诊断的、FIGO分期III-IV期的高级别浆液性或子宫内膜样卵巢癌患者，完成一线化疗并取得CR或PR后按照 2:1的比例随机接受塞纳帕利（270例）或安慰剂（133例）治疗，其中有1例未接受化疗后的进一步治疗。主要研究终点是盲态独立中心审查（BICR）评估的无进展生存期（PFS）。结果显示，与安慰剂相比，塞纳帕利显著改善了患者PFS（未达到 vs. 13.6个月，HR=0.43，95%CI：0.32-0.58；P<0.0001）；BRCA突变组（未达到 vs. 15.6个月，HR=0.43，95%CI：0.24-0.76）和BRCA未突变组（未达到 vs. 12.9个月，HR=0.43，95%CI：0.30-0.61）的PFS都得到显著改善。其次，塞纳帕利在具有同源重组缺陷（HRD：未达到 vs. 15.7个月，HR=0.36，95%CI：0.22-0.61）和同源重组修复正常（HRP：27.1个月 vs. 19.5个月，HR=0.74，95%CI：0.36-1.54）亚组的患者中均显示出显著PFS获益，突显其广泛的临床应用潜力。此研究结果将有力支持塞纳帕利单药作为新诊断卵巢癌患者一线全人群维持治疗的标准方案。 FLAMES研究数据 10. Sotorasib/ 商品名：Lumakras 通用名：Sotorasib 适应症：联合帕尼单抗用于携带KRAS G12C突变的经治转移性结直肠癌临床试验：CodeBreaK 300 原研公司：Amgen 获批日期：2025.01.16 获批机构：FDA 2025年1月16日，FDA批准Sotorasib联合帕尼单抗用于治疗经检测确定为KRAS G12C突变的转移性结直肠癌（mCRC）成人患者，这些患者之前曾接受过基于氟尿嘧啶、奥沙利铂和伊立替康的化疗。当日，FDA还批准了therascreen KRAS RGQ PCR Kit（QIAGEN GmbH生产）作为伴随诊断，用于筛选结直肠癌患者中携带KRAS G12C突变、可能适合接受Sotorasib联合帕尼单抗治疗的患者。2024年6月，FDA加速批准Adagrasib联合西妥昔单抗治疗KRAS G12C突变型局部晚期或转移性结直肠癌患者，这些患者既往接受过氟尿嘧啶、奥沙利铂和伊立替康为基础的化疗。此次获批将为携带KRAS G12C突变的结直肠癌患者带来更多治疗方案。本次获批基于一项随机、开放标签、对照试验CodeBreaK 300（NCT05198934），旨在评估Sotorasib+帕尼单抗在既往接受过基于氟嘧啶、奥沙利铂和伊立替康化疗的携带KRAS G12C突变转移性结直肠癌患者中的疗效。研究纳入160名患者，被随机分配（1：1：1）接受Sotorasib（每日一次口服：960mg）+帕尼单抗（每两周注射一次：6mg/kg）、Sotorasib（每日一次口服：240mg）+帕尼单抗（每两周注射一次：6mg/kg）或研究者选择的标准护理（SOC：曲氟尿苷/替匹嘧啶或瑞戈非尼）。主要疗效结局指标是盲法独立中心审查（BICR）根据RECIST v1.1评估的无进展生存期（PFS），其他疗效结局指标包括总生存期（OS）、总缓解率（ORR）和缓解持续时间（DOR）。结果显示，Sotorasib（每日一次口服：960mg）+帕尼单抗（每两周注射一次：6mg/kg）治疗组的中位PFS显著优于SOC组（5.6个月 vs. 2个月，HR=0.48，95%CI：0.3-0.78），而OS最终分析结果未达到统计学显著性。此外，Sotorasib（每日一次口服：960mg）+帕尼单抗（每两周注射一次：6mg/kg）治疗组的ORR高于SOC组（26% vs. 0%），Sotorasib（每日一次口服：960mg）+帕尼单抗（每两周注射一次：6mg/kg）治疗组的中位DOR为4.4个月，SOC组的中位DOR没有数据。与SOC组相比，随机分配到Sotorasib（每日一次口服：240mg）+帕尼单抗（每两周注射一次：6 mg/kg）组治疗患者的PFS最终分析无统计学意义。 CodeBreaK 300研究数据 11. Datopotamab deruxtecan/ 商品名：Datroway 通用名：Datopotamab deruxtecan 适应症：HR阳性、HER2阴性（IHC 0、IHC 1+或IHC 2+/ISH-）不可切除或转移性乳腺癌临床试验：TROPION-Breast01 原研公司：第一三共、阿斯利康获批日期：2025.01.17 获批机构：FDA 2025年1月17日，FDA批准Datopotamab deruxtecan用于治疗既往接受过内分泌治疗和化疗的HR阳性、HER2阴性（IHC 0、IHC 1+或IHC 2+/ISH-）不可切除或转移性乳腺癌成人患者。Datopotamab deruxtecan是一款靶向Trop-2的DNA拓扑异构酶I抑制剂（DXd）抗体偶联药物（ADC），由第一三共与阿斯利康共同开发。这是全球第二款获得FDA批准上市的Trop-2 ADC。本次获批基于一项多中心、开放性、随机试验TROPION-Breast01（NCT05104866），研究纳入732例既往接受过内分泌治疗和化疗的HR阳性、HER2阴性（IHC 0、IHC 1+或IHC 2+/ISH-）不可切除或转移性乳腺癌患者，旨在评估Datopotamab deruxtecan（365例）与研究者选择的单药化疗（367例）在这些患者中的疗效和安全性。试验的主要疗效结果为经盲态独立中心（BICR）评估的无进展生存期（PFS）和总生存期（OS），其他疗效结果为BICR评估的客观缓解率（ORR）和缓解持续时间（DOR）。结果显示，对比化疗组，Datopotamab deruxtecan治疗组可将患者的疾病进展或死亡风险降低37%（HR=0.63，95%CI：0.52-0.76；P<0.0001）。Datopotamab deruxtecan治疗组患者的中位PFS优于化疗组（6.9个月 vs. 4.9个月），中位OS也高于化疗组（18.6个月 vs. 18.3个月）；此外，Datopotamab deruxtecan组和化疗组的ORR分别为36%和23%，中位DOR分别为6.7个月和5.7个月。 TROPION-Breast01研究数据 12. 塔戈利单抗/ 商品名：科泰莱通用名：塔戈利单抗适应症：复发性或转移性鼻咽癌患者的一线治疗临床试验：KL167-Ⅲ-08 原研公司：科伦博泰获批日期：2025.01.20 获批机构：NMPA 2025年1月20日，NMPA批准塔戈利单抗联合吉西他滨和顺铂用于复发性或转移性鼻咽癌患者的一线治疗。此次获批，意味着塔戈利单抗在鼻咽癌治疗领域的应用范围进一步扩大。2024年12月31日，NMPA已批准塔戈利单抗用于既往接受过二线及以上化疗失败的复发或转移性鼻咽癌患者的治疗。塔戈利单抗是一种靶向PD-L1的创新人源化IgG1κ亚型单克隆抗体，通过特异性地与PD-L1结合，抑制PD-L1/PD-1的相互作用，解除PD-1/PD-L1信号通路介导的免疫抑制，促进T细胞的增殖和细胞因子的分泌，从而增强肿瘤免疫反应。本次获批基于一项多中心、双盲、安慰剂对照的III期临床试验KL167-Ⅲ-08（NCT05294172/CTR20220691），研究纳入295例既往未经治疗的复发性或转移性鼻咽癌患者，旨在评估塔戈利单抗联合化疗（顺铂和吉西他滨，197例）与安慰剂联合化疗（顺铂和吉西他滨，98例）治疗复发性或转移性鼻咽癌的疗效和安全性。主要研究终点为独立评审委员会（IRC）采用RECIST v1.1评价的无进展生存期（PFS）。结果显示，截至2024年2月4日，中位随访时间为11.7个月，塔戈利单抗联合化疗组和安慰剂联合化疗组的中位PFS为分别为未达到和7.9个月（HR=0.47，95%CI：0.33-0.66，P＜0.0001），显著降低患者疾病进展或死亡风险53%；对比安慰剂联合化疗组，塔戈利单抗联合化疗组延长了患者的中位缓解持续时间（DOR）近一倍（11.7个月 vs. 5.8个月）；同时显著提升了患者的客观缓解率（ORR：81.7% vs. 74.5%）。 KL167-Ⅲ-08研究数据 13. 德曲妥珠单抗/ 商品名：优赫得、Enhertu 通用名：德曲妥珠单抗、Trastuzumab Deruxtecan 适应症：HR阳性、HER2低表达（IHC 1+或IHC 2+/ISH-）或HER2超低表达（IHC 0，伴膜染色）不可切除或转移性乳腺癌临床试验：DESTINY-Breast06 原研公司：阿斯利康、第一三共获批日期：2025.01.27 获批机构：FDA 2025年1月27日，FDA批准德曲妥珠单抗用于治疗在转移阶段接受过至少一种内分泌治疗的HR阳性、HER2低表达（IHC 1+或IHC 2+/ISH-）或HER2超低表达（IHC 0，伴膜染色）不可切除或转移性乳腺癌成人患者。此前，德曲妥珠单抗已经获批用于HER2阳性（IHC 3+或ISH+）和HER2低表达（IHC1+或IHC2+/ISH-）的乳腺癌患者，本次获批将适用病患群体扩展至HER2超低表达（IHC 0，伴膜染色）类型。本次获批基于一项随机、多中心、开放标签的III期临床试验DESTINY-Breast06（NCT04494425），研究纳入866例在转移阶段接受过至少一种内分泌治疗的HR阳性、HER2低表达（IHC 1+或IHC 2+/ISH-）或HER2超低表达（IHC 0，伴膜染色）不可切除或转移性乳腺癌成人患者。HER2低表达人群和总体人群（HER2低表达和HER2超低表达）中患者分别随机1：1分配至德曲妥珠单抗治疗组和化疗治疗组。主要疗效结果指标是BICR根据RECIST v1.1评估的HER2低表达乳腺癌患者的中位无进展生存期（mPFS），其他疗效结果指标是BICR根据RECIST v1.1评估的总体人群mPFS、HER2低表达患者的总生存期（OS）和总体人群的OS。结果显示，HER2低表达患者接受德曲妥珠单抗和化疗治疗的mPFS分别为13.2个月和8.1个月，客观缓解率（ORR）分别为62%和35.2%；总体人群接受德曲妥珠单抗和化疗治疗的mPFS分别为13.2个月和8.1个月；ORR分别为62.6%和34.4%。针对153例HER2超低表达患者的探索性分析，随机接受德曲妥珠单抗和化疗治疗的mPFS分别为15.1个月和8.3个月，ORR分别为65.7%和30.8%。 DESTINY-Breast06研究数据 14. 菲诺利单抗/ 商品名：安佑平通用名：菲诺利单抗适应症：复发性和/或转移性头颈部鳞状细胞癌临床试验：NCT04146402 原研公司：神州细胞获批日期：2025.02.08 获批机构：NMPA 2025年2月8日，NMPA批准菲诺利单抗联合含铂化疗用于复发性和/或转移性头颈部鳞状细胞癌的一线治疗。菲诺利单抗（SCT-I10A）是神州细胞自主研发的重组人源化抗PD-1 IgG4型单克隆抗体注射液，也是首个获批治疗头颈部鳞癌的国产PD-1单抗。本次获批基于一项随机、双盲的III期临床试验NCT04146402，研究纳入370例符合条件的复发性和/或转移性头颈部鳞状细胞癌患者，随机2：1分配至菲诺利单抗+化疗（顺铂+5-氟尿嘧啶）治疗组和安慰剂+化疗治疗组，主要终点是总生存期（OS）。结果显示，对比安慰剂+化疗治疗，菲诺利单抗+化疗治疗显著改善了患者OS（14.1个月 vs. 10.5个月，HR=0.73，95%CI：0.57-0.95，P=0.0165）；其次，菲诺利单抗+化疗组和安慰剂+化疗组的中位无进展生存期（PFS）分别为5.8个月和5.6个月，客观缓解率（ORR）分别为39.9%和29.4%，中位缓解持续时间（DOR）分别为19.3个月和5.0个月。安全性方面，98.9%（366/370）的患者出现了治疗相关不良事件（TEAE），菲诺利单抗+化疗组和安慰剂+化疗组的TEAE发生率分别为67.2%和54.5%，TEAE为食欲下降、恶心、甲状腺功能减退、皮炎、低钾血症和甲状腺功能亢进等。 NCT04146402研究数据 15. 埃万妥单抗/ 商品名：锐珂通用名：埃万妥单抗适应症：联合卡铂和培美曲塞用于EGFR 20ins突变的局部晚期或转移性NSCLC 临床试验：PAPILLON 原研公司：强生获批日期：2025.02.11 获批机构：NMPA 2025年2月11日，NMPA批准埃万妥单抗联合卡铂和培美曲塞用于EGFR 20号外显子插入突变（EGFR 20ins）的局部晚期或转移性NSCLC成人患者的一线治疗。埃万妥单抗是一款EGFR/MET双特异性抗体疗法，它除了能够阻断EGFR和MET介导的信号传导以外，还可以引导免疫细胞靶向携带激活性和抗性EGFR/MET突变和扩增的肿瘤。本次获批基于一项随机、开放标签的III期临床试验PAPILLON（NCT04538664），研究纳入308例未经治疗的携带EGFR 20ins突变的局部晚期或转移性NSCLC患者，随机1：1分配到埃万妥单抗+化疗（卡铂和培美曲塞，n=153）组和化疗组（n=155），主要疗效结果指标是BICR根据RECIST v1.1评估的无进展生存期（PFS），次要疗效结果指标是客观缓解率（ORR）、总生存期（OS）和持续缓解时间（DOR）。结果显示，对比化疗组，BICR评估埃万妥单抗+化疗组显著提高患者的中位PFS（11.4个月 vs. 6.7个月）；截至数据统计时，埃万妥单抗+化疗组和化疗组的ORR分别为73%和47%，埃万妥单抗+化疗组的中位OS显著优于化疗组（未达到 vs. 24.4个月，HR=0.67，95%CI：0.42-1.09，P=0.11），埃万妥单抗+化疗组和化疗组的中位DOR分别为9.7个月和4.4个月。 PAPILLON研究数据 16. Mirdametinib/ 商品名：Gomekli 通用名：Mirdametinib 适应症：1型神经纤维瘤病相关丛状神经纤维瘤（NF1-PN）成人和2岁及以上儿童患者临床试验：ReNeu 原研公司：SpringWorks 获批日期：2025.02.12 获批机构：FDA 2025年2月12日，FDA批准Mirdametinib用于治疗无法完全切除的1型神经纤维瘤病相关丛状神经纤维瘤（NF1-PN）成人和2岁及以上儿童患者。神经纤维瘤病（NF1）是一种遗传性疾病，患者一生中约有30%至50%的风险发展为丛状神经纤维瘤（PN），这种肿瘤沿着外周神经鞘以浸润性方式生长，可能导致严重容貌畸形、疼痛和功能障碍。PN还可能转变为恶性外周神经鞘瘤，这是一种侵袭性且可能致命的疾病。由于PN沿神经浸润性生长，其外科切除十分具有挑战性，高达约85%的丛状神经纤维瘤被认为无法完全切除。Mirdametinib是一种口服别构小分子MEK抑制剂，靶向MEK1和MEK2。Mirdametinib是首个获批可同时用于治疗成人和儿童NF1-PN的药物，有望成为儿童NF1-PN患者的“best-in-class”疗法。本次获批基于一项多中心、单臂临床试验ReNeu（NCT03962543），研究纳入114名年龄不低于2岁的无法完全切除的NF1-PN患者（其中成人58例、儿童患者56例），以上患者接受Mirdametinib治疗。主要疗效终点指标为经确认的总体缓解率（ORR），缓解情况通过BICR采用磁共振成像（MRI）体积分析法进行评估，依据修订后的神经纤维瘤病和神经鞘瘤病反应评估（REiNS）标准，并在24个周期的治疗阶段中通过2-6个月内的后续肿瘤评估确认；次要疗效结果指标为持续缓解时间（DOR）。结果显示，成人患者接受Mirdametinib治疗经确认的ORR为41%，儿童患者接受Mirdametinib治疗经确认的ORR为52%；在确认获得缓解的患者中，88%的成人和90%的儿童患者的DOR≥12个月，且50%的成人患者和48%的儿童患者的DOR≥24个月。 ReNeu研究数据声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

临床3期临床结果上市批准加速审批

2024-09-11

·GlobeNewswire-Health Care

BriaCell Reports Positive Overall Survival (OS) in Metastatic Breast Cancer

Median overall survival of 15.6 months in Phase 2 Bria-IMT™ study patients treated in combination with immune checkpoint inhibitorOS of 15.6 months compares favorably with 6.7-9.3 months reported for similar patients in the literatureOngoing Phase 3 study investigating Bria-IMT™ in similar metastatic breast cancer populationNo drug related discontinuations to date PHILADELPHIA and VANCOUVER, British Columbia, Sept. 11, 2024 (GLOBE NEWSWIRE) -- BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, is pleased to announce positive overall survival data of its Phase 2 clinical study of Bria-IMT™ in combination with an immune check point inhibitor (CPI) in late stage metastatic breast cancer. Median overall survival of 15.6 months is reported in BriaCell’s most recent patients (treated since 2022) vs. 6.7-9.3 months for similar patients reported in the literature (see table below). These patients are being treated with the same Bria-IMT™ formulation currently being used in BriaCell’s ongoing Phase 3 pivotal study in metastatic breast cancer (listed on ClinicalTrials.gov as NCT06072612) and represent patients enrolled post-COVID when full study activities resumed. This represents a substantial improvement over BriaCell’s 13.4 months median overall survival previously reported in December 2023. “Overall survival in patients with heavily pre-treated metastatic breast cancer is very poor,” stated Sara A. Hurvitz, MD, Professor of Medicine, Fred Hutch Cancer Center and University of Washington and BriaCell medical advisory board member. “The BriaCell early data is quite encouraging from both efficacy and tolerability standpoints.” “We wanted to look at the Phase 2 data of those patients who most closely resemble the patients being treated in our ongoing phase 3 study and compare them to similar patients in the literature,” stated Dr. William V. Williams, BriaCell’s President and CEO. “The nearly two-fold overall survival benefit we are seeing with the Bria-IMT™ regimen, together with the similar previously reported approximate doubling of progression free survival, compared with literature controls, strongly support our belief that Bria-IMT™ could have a meaningful impact in the lives of heavily pre-treated metastatic breast cancer patients. We look forward to further clinical development of Bria-IMT™ with the goal of establishing it as a new standard of care for patients with metastatic breast cancer.” “The Bria-IMT™ regimen is the only investigational drug we have seen to show these impressive survival numbers in heavily pre-treated metastatic breast cancer patients who have failed numerous prior treatments including immune check point inhibitors and antibody drug conjugates,” stated Giuseppe Del Priore, MD, MPH, BriaCell’s Chief Medical Officer. “These survival and clinical benefit data support BriaCell’s hypothesis of additive and/or synergistic effects of immune check point inhibitors with Bria-IMT™ and drive the ongoing pivotal study of our combination regimen in the treatment of metastatic breast cancer.” The Phase 2 study enrolled 54 heavily pre-treated metastatic breast cancer patients (average number of prior treatments = 6) who were treated with the Bria-IMT™ regimen and an immune checkpoint inhibitor. Of these 54 patients, 37 were treated with the Phase 3 formulation and 25 of these were treated post-COVID when full study activities resumed. This data represents an additional six months of follow-up of the survival data presented at the San Antonio Breast Cancer Symposium in December 2023. Table 1. Comparative Median Overall Survival (OS) and Progression-Free Survival (PFS) in Similar Patients (Interim Analysis Using Kaplan-Meier Estimate) StudyPrior Lines of Therapy (median, range)Number of PatientsOS (months)PFS (months) BriaCell’s Phase 2 study patients who received pivotal Phase 3 study formulation (since 2022)5.5 (2-13)2515.64.1 BriaCell’s Phase 2 study patients who received pivotal Phase 3 study formulation (total)6 (2-13)3713.43.9 Bardia, A. et. al. 1 (TNBC)4 (2-14)2626.91.7 Tripathy D. et. al. 2 (Brain metastases)≥4 in 91%1787.5-7.81.9-2.8 O’Shaughnessy J. et. al. 3non-TNBC at initial diagnosis5 (2-14)766.72.3 O’Shaughnessy J. et. al. 3TNBC at initial diagnosis4 (2-10)1576.91.6 Cortes et. al. 44 (0-13)5949.1-9.31.9-2.5 References Bardia A, et al. Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression. J Clin Oncol. 2024 May 20;42(15):1738-1744. doi: 10.1200/JCO.23.01409. Epub 2024 Feb 29. PMID: 38422473.Tripathy D, et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022;8(7):1047-1052. doi:10.1001/jamaoncol.2022.0514.O’Shaughnessy J et al. Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2022 Sep;195(2):127-139. doi: 10.1007/s10549-022-06602-7. Epub 2022 May 11. PMID: 35545724; PMCID: PMC9374646.Cortes J, Perez-Garcia J, Levy C, Gómez Pardo P, Bourgeois H, Spazzapan S, Martínez-Jañez N, Chao TC, Espié M, Nabholtz JM, Gonzàlez Farré X, Beliakouski V, Román García J, Holgado E, Campone M. Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2018 Apr 1;29(4):881-887. doi: 10.1093/annonc/mdy051. PMID: 29481630. About BriaCell Therapeutics Corp. BriaCell is a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care. More information is available at https://briacell.com/. Safe Harbor This press release contains “forward-looking statements” that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements, including statements about: the impact of Bria-IMT™ on patients with metastatic breast cancer; BriaCell’s further clinical development of Bria-IMT™; and the efficacy of immune check point inhibitors, are based on BriaCell’s current expectations and are subject to inherent uncertainties, risks, and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully under the heading “Risks and Uncertainties” in the Company’s most recent Management’s Discussion and Analysis, under the heading “Risk Factors” in the Company’s most recent Annual Information Form, and under “Risks and Uncertainties” in the Company’s other filings with the Canadian securities regulatory authorities and the U.S. Securities and Exchange Commission, all of which are available under the Company’s profiles on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov. Forward-looking statements contained in this announcement are made as of this date, and BriaCell Therapeutics Corp. undertakes no duty to update such information except as required under applicable law. Neither the Toronto Stock Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Toronto Stock Exchange) accepts responsibility for the adequacy or accuracy of this release. Contact Information Company Contact:William V. Williams, MDPresident & CEO1-888-485-6340info@briacell.com Media Relations:Jules AbrahamCORE IRjulesa@coreir.com Investor Relations Contact:CORE IRinvestors@briacell.com

临床3期免疫疗法临床2期临床结果

2024-09-04

·echemi

New Bladder Cancer Drug Vemurafenib Extends Survival by Over Half a Year, But Side Effects Occur in Over 90% of Patients!

Astellas Pharmaceutical Group (Tokyo Stock Exchange: 4503, President and Chief Executive Officer: Naoki Okamura, "Astellas") announced on August 20 that the Center for Drug Evaluation (CDE) of the China National Drug Administration has approved Vientumab for injection (trade name: Vientumab is indicated for the treatment of locally advanced or metastatic uroepithelial carcinoma (mUC) in adult patients who have previously received platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors. Urothelial carcinoma is a serious and common cancer that affects the lower urinary tract (including the bladder and urethra) as well as the upper urinary tract (including the ureters and renal pelvis). In 2022, more than 92,000 patients in China were diagnosed with bladder cancer, of which about 41,000 patients sadly died. Survival rates are particularly poor for patients with advanced or metastatic urothelial cancer, so new treatments are urgently needed to extend patients' lives. Professor Guo Jun, Director of the Department of Melanoma and Sarcoma and Urologic Oncology, Peking University Cancer Hospital, pointed out: "On August 13, 2024, the National Medical Products Administration (NMPA) officially approved Vientumab for injectable use in adult patients with locally advanced or metastatic uroepithelial carcinoma who have previously received platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors. The approval is based on a global Phase 3 registration study and a bridging study in the Chinese population. This is a landmark event that marks the accessibility of new antibody-drug conjugate (ADC) therapies for the entire population of UC." Ahsan Arozullah, MD, MPH, senior vice president and head of oncology area Development at Astellas, said: "We are committed to driving scientific advances that will significantly change the course of cancer care around the world. The approval of Veentumab by the Center for Drug Evaluation (CDE) of the China National Drug Administration provides another treatment option for patients with locally advanced or metastatic urothelial carcinoma in China, and patients are expected to have better treatment outcomes as a result." Data from the global study EV-301 and its Chinese bridging study EV-203 support CDE's approval of Veentumab. The randomized Phase 3 study EV-301 supports the worldwide registration of Veentumab. The EV-203 study (NCT04995419) is a single-arm, open-label, multicenter phase 2 study in Chinese patients with locally advanced or metastatic uroepithelial carcinoma who have previously been treated with PD-1/PD-L1 inhibitors and platinum-containing chemotherapy. The results showed that EV-203 met its primary endpoint, which was a confirmed objective response rate (ORR) as assessed by an Independent Review Committee (IRC) in patients treated with Veentumab monotherapy compared to historical controls (37.5% [n/N=15/40; 95% confidence interval: 22.7-54.2]) was statistically significant. Efficacy and pharmacokinetic data from the study were consistent with global data, and safety results showed mostly grade 1-2 treatment-related adverse events. Astellas has already reflected the impact of the approval of Veentumab in China in its financial forecast for fiscal year 2024 (ending March 31, 2025). About the EV-203 study The Phase II clinical trial of EV-203 (NCT04995419) is a multicenter, single-arm bridging study conducted in China to evaluate the efficacy, safety, and pharmacokinetics of Veentumab in Chinese patients. The study included a total of 40 patients with locally advanced or metastatic urothelial carcinoma who had previously been treated with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. The primary endpoint of the trial was met, and the confirmed objective response rate in patients treated with Veentumab monotherapy was 37.5% as assessed by an independent review board (n/N=15/40, 95% confidence interval [CI] : 22.7-54.2). Of these, 1 patient achieved a complete response (2.5%) and 14 patients achieved a partial response (35%). No new safety signals were found in the study. The majority of veentumab treatment-related adverse events were grade 1-2, with 2 patients discontinuing treatment due to treatment-related adverse events (acute coronary syndrome and hyperglycemia/rash). About the EV-301 study The EV-301 clinical trial (NCT03474107) is a global multicenter, open, randomized Phase III trial designed to evaluate the efficacy of Veentutuzumab compared to chemotherapy (docetaxel, paclitaxel, or vinflunine). Efficacy and safety in the treatment of 608 patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and PD-1/L1 inhibitors. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and disease control rate (DCR), as well as safety/tolerability and quality of life parameters. The EV-301 study showed that median overall survival was longer in the veentumab group than in chemotherapy (12.88 and 8.97 months, respectively; Risk ratio: 0.70; 95% confidence interval: 0.56 to 0.89; p=0.001), the progression-free survival was also longer than that in the chemotherapy group (5.55 months vs. 3.71 months, respectively; Hazard ratio: 0.62; 95% confidence interval: 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar between the two groups (93.9% in the veentumab group and 91.8% in the chemotherapy group). The incidence of grade 3 and above adverse events was also similar in both groups (51.4% and 49.8%, respectively). The results were published in the New England Journal of Medicine. About bladder cancer and urothelial cancer Urothelial cancer, or bladder cancer, originates in urothelial cells, which are found in the urethra, bladder, ureter, renal pelvis, and some other organs. Urothelial carcinoma accounts for 90% of all bladder cancer cases and may also occur in the renal pelvis, ureter and urethra. If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease. If the tumor has spread to other parts of the body, it is called metastatic disease. About 12% of cases have locally advanced or metastatic urothelial carcinoma at diagnosis. In China, the incidence of bladder cancer ranked 11th among all cancers in 2022, with more than 92,000 new cases estimated that year. The five-year prevalence of bladder cancer in China is estimated at 2.5 per 100,000 cases, or 276,102 cases. Continuous treatment and monitoring make bladder cancer one of the most expensive cancers to treat, with the highest costs compared to other malignancies. About Bexoft (generic name Vientumab for injection) Veentumab is a first-of-its-kind antibody-drug conjugate (ADC) that targets the Nectin-4 protein, which is expressed on the cell surface and is highly expressed in bladder cancer. Non-clinical studies have shown that by binding to cells expressing the Nectin-4 protein, the anti-tumor component monomethyloratatin E (MMAE) is internalized and released into cells, causing cell proliferation arrest (cell cycle arrest) and programmed cell death (apoptosis), thereby exerting its anticancer activity. Ongoing research The EV-302 clinical trial (NCT04223856) is an open-label, randomized, controlled Phase 3 clinical trial designed to evaluate the combination of veentutuzumab and pabolizumab compared to platinum-containing chemotherapy. Efficacy in patients with untreated locally advanced or metastatic urothelial carcinoma (la/mUC) suitable for cisplatin or carboplatin therapy is not limited by PD-L1 expression. The EV-103 clinical trial (NCT03288545) is an ongoing multi-cohort, open-label, multi-center phase 1b/2 clinical trial. To investigate the efficacy of veentuzumab alone or in combination with pabolizumab and/or chemotherapy in the treatment of first - or second-line locally advanced or metastatic urothelial carcinoma and in patients with myoinvasive bladder cancer (MIBC). The EV-104 trial (NCT05014139) is a Phase 1 study designed to explore the feasibility of using Veentumab in patients with non-myoinvasive bladder cancer (NMIBC). The study was divided into two parts, evaluating dose escalation and dose extension of veentumab as postoperative monotherapy. Studies of the combination of Vientumab and pabolizumab in different stages of uroepithelial cancer, including two Phase 3 trials EV-304 (NCT04700124, also known as the KEYNOTE-B15 trial) and EV-303 (NCT03924895, also known as the KEYNOTE-905 trial), Both were targeted at muscular invasive bladder cancer. The EV-202 trial (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter phase 2 clinical trial investigating the efficacy of Veentumab alone in previously treated patients with advanced solid tumors. The trial also included a cohort studying the combination of veentuzumab and pabolizumab in previously untreated relapsed and metastatic head and neck squamous cell carcinoma. About Astellas Astellas Pharmaceutical Group is a global pharmaceutical company with operations in more than 70 countries and regions. The company is pursuing a "Focus Area Approach" to address unmet medical needs by focusing on physiological mechanisms and treatments to identify opportunities for continued development of new drugs. At the same time, the company is looking beyond prescription drugs to create Rx+® medical solutions by combining expertise and knowledge with cutting-edge technology from external partners in different fields. Through these efforts, Astellas is committed to being at the forefront of the ever-changing healthcare industry, translating scientific advances into value for patients. More detailed information, please visit the website https://www.astellas.com/en. About Astellas' partnership with Pfizer Astellas and Pfizer jointly develop and commercialize Veentumab on a 50:50 basis worldwide. In the United States, Astellas and Pfizer jointly promote PADCEV® (enfortumab vedotin-ejfv). Pfizer is responsible for the commercialization and registration of the product in the Americas (excluding the United States). Astellas is responsible for the commercialization and registration of the product outside the Americas.

临床结果临床3期临床2期上市批准临床1期

100 项与酒石酸长春氟宁相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	酒石酸长春氟宁	L01CA05	DB11641

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
膀胱癌	以色列	Pierre Fabre SA	2013-10-11
尿路上皮癌	欧盟	Pierre Fabre Médicament SAS	2009-09-21
尿路上皮癌	冰岛	Pierre Fabre Médicament SAS	2009-09-21
尿路上皮癌	列支敦士登	Pierre Fabre Médicament SAS	2009-09-21
尿路上皮癌	挪威	Pierre Fabre Médicament SAS	2009-09-21

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适应症	最高研发状态	国家/地区	公司	日期
头颈癌转移	临床3期	法国	Pierre Fabre Medicament Information	2014-04-25
复发性头颈癌	临床3期	法国	Pierre Fabre Medicament Information	2014-04-25
转移性头颈部鳞状细胞癌	临床3期	法国	Pierre Fabre Medicament Information	2014-04-25
转移性肿瘤	临床3期	阿根廷	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	奥地利	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	白俄罗斯	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	比利时	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	法国	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	德国	Pierre Fabre Medicament Information	2009-07-01
转移性肿瘤	临床3期	意大利	Pierre Fabre Medicament Information	2009-07-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02057913 (VinCaP, Pubmed \| Br J Cancer)	临床2期	阴茎鳞状细胞癌一线	-	Vinflunine 320 mg/m2	積蓋願膚構淵鬱製蓋鹽(窪襯鹽衊壓製鹽衊淵觸) = 構鬱網膚膚膚齋築齋範醖遞觸衊範繭淵鏇範憲 (築範顧遞艱襯鏇積憲鬱 ) 更多	-	2022-01-01
ASCO2020	N/A	转移性尿路上皮癌二线	70	vinflunine (Low SII)	繭範衊簾淵觸鑰廠餘遞(網衊願齋齋窪鹽夢鬱艱): HR = 0.6 (95% CI, 0.36 ~ 1.0), P-Value = 0.0312 更多	-	2020-05-25
				vinflunine (High SII)
NCT02665039 (VINGEM, Pubmed)	临床2期	晚期尿路上皮癌一线	62	Vinflunine/gemcitabine	獵選艱艱選鏇夢廠簾醖(鬱糧衊窪淵獵膚淵餘製) = 艱繭壓顧願鏇廠衊願窪憲蓋簾築窪襯壓構艱廠 (艱鏇遞襯夢積獵窪獵築 ) 更多	不佳	2020-03-01
				Carboplatin/gemcitabine	獵選艱艱選鏇夢廠簾醖(鬱糧衊窪淵獵膚淵餘製) = 遞顧膚鏇構顧顧積鹹網憲蓋簾築窪襯壓構艱廠 (艱鏇遞襯夢積獵窪獵築 ) 更多
NCT01091168 (L00070 IN 308 B0, CTgov)	临床3期	转移性肿瘤 \| 转移性乳腺癌	594	Vinflunine (Vinflunine)	獵憲廠膚築築齋構齋觸(艱齋獵膚鑰窪窪鏇構餘) = 齋簾襯壓範夢願鬱網鏇鹹夢願製襯遞鹽膚遞膚 (廠簾艱遞鹹糧鏇齋蓋壓, 憲構構願遞衊獵鬱觸鑰 ~ 廠餘憲積膚範鹽築鬱觸) 更多	-	2019-09-16
				mitomycin C+cyclophosphamide+carboplatin+melphalan+cisplatin+thiotepa (Alkylating Agent)	獵憲廠膚築築齋構齋觸(艱齋獵膚鑰窪窪鏇構餘) = 鏇製憲積蓋醖獵糧築壓鹹夢願製襯遞鹽膚遞膚 (廠簾艱遞鹹糧鏇齋蓋壓, 構艱選餘膚簾廠夢網窪 ~ 鹽網鑰遞廠築蓋簾顧遞) 更多
NCT01095003 (CTgov)	临床3期	晚期乳腺癌	770	Vinflunine+Capecitabine (Vinflunine Plus Capecitabine)	壓淵獵醖網構積鹹鏇衊(壓齋構簾糧網製鏇製顧) = 選蓋憲鏇齋淵構淵繭築鬱窪簾鑰顧製獵壓廠襯 (鏇衊膚窪選壓遞齋淵蓋, 範淵齋網選顧網膚廠構 ~ 積餘鏇淵獵製廠糧鑰齋) 更多	-	2019-09-13
				Capecitabine (Capecitabine Single-agent)	壓淵獵醖網構積鹹鏇衊(壓齋構簾糧網製鏇製顧) = 衊製膚觸窪獵餘獵淵艱鬱窪簾鑰顧製獵壓廠襯 (鏇衊膚窪選壓遞齋淵蓋, 鬱壓鬱顧鏇憲製餘願糧 ~ 顧構鏇襯衊繭遞憲顧遞) 更多
NCT02054338 (VICTORIA, CTgov)	临床3期	局部晚期乳腺癌 \| 转移性乳腺癌 \| 晚期乳腺癌	1,004	Vinflunine+Gemcitabine (Vinflunine Plus Gemcitabine)	獵獵艱艱鏇艱鏇鹹鬱選(膚鹽獵構襯繭淵廠膚窪) = 夢襯夢鹽壓憲糧繭構憲憲膚構壓鹽選襯廠淵遞 (網網艱壓簾糧壓積獵艱, 鹹膚鹹鑰遞鏇壓顧網餘 ~ 淵簾壓鹹蓋襯齋蓋鑰鏇) 更多	-	2019-08-28
				Paclitaxel+Gemcitabine (Paclitaxel Plus Gemcitabine)	獵獵艱艱鏇艱鏇鹹鬱選(膚鹽獵構襯繭淵廠膚窪) = 憲鬱簾壓餘範簾齋鬱餘憲膚構壓鹽選襯廠淵遞 (網網艱壓簾糧壓積獵艱, 網製齋鏇醖範構積醖餘 ~ 鏇壓網蓋積廠網獵鬱遞) 更多
NCT01844947 (Vinsor, Pubmed \| Oncologist) 人工标引	临床1期	转移性尿路上皮癌	22	Vinflunine+Sorafenib	簾簾鹹積範繭淵艱鏇窪(蓋壓繭範襯積淵鬱淵範) = vinflunine 280 mg/m2 plus sorafenib 400 mg 壓淵構網衊艱願齋網積 (願選鹹壓鏇鹽觸壓夢願 ) 更多	积极	2019-06-01
NCT02256436 (KEYNOTE-045 \| 3475-045 \| MK-3475-045, Pubmed \| Ann Oncol)	临床3期	复发性尿路上皮癌二线	542	Pembrolizumab	襯製積製築憲願蓋鹹願(顧衊鑰鏇鏇製顧淵積簾) = 壓鹽構淵膚憲繭選築鏇簾醖鹽鹹憲簾顧壓鏇膚 (膚淵繭襯觸繭製鑰選鬱 ) 更多	积极	2019-06-01
				Paclitaxel	襯製積製築憲願蓋鹹願(顧衊鑰鏇鏇製顧淵積簾) = 壓觸築艱獵淵鑰齋蓋鏇簾醖鹽鹹憲簾顧壓鏇膚 (膚淵繭襯觸繭製鑰選鬱 ) 更多
NCT01953003 (CTgov)	临床3期	晚期乳腺癌	112	vinflunine+capecitabine	醖襯遞網蓋鑰壓鬱夢鑰 = 壓齋艱鹹構積製製範顧糧顧觸廠憲夢醖鏇築遞 (網窪襯淵簾夢鹹遞醖構, 繭築簾築鏇醖齋築鏇憲 ~ 顧夢簾顧襯鹹壓淵獵壓) 更多	-	2019-05-02
NCT02347332 (CTgov)	临床3期	复发性头颈癌 \| 转移性头颈部鳞状细胞癌 \| 头颈癌转移	459	Vinflunine (Vinflunine Plus Methotrexate)	遞願選廠鑰鏇遞齋顧憲(範觸窪齋鏇範餘膚構衊) = 蓋廠鹹積鑰餘艱夢膚網積鑰憲願襯觸構醖齋鬱 (觸製醖願鹹網廠簾製鹹, 積鬱淵壓廠淵衊積積糧 ~ 醖鹹鬱蓋憲顧觸構襯蓋) 更多	-	2019-02-04
				Methotrexate (Methotrexate)	遞願選廠鑰鏇遞齋顧憲(範觸窪齋鏇範餘膚構衊) = 鹹鑰壓餘製鏇製願鹽糧積鑰憲願襯觸構醖齋鬱 (觸製醖願鹹網廠簾製鹹, 網鑰襯網廠範餘獵憲襯 ~ 鹽顧壓廠構襯窪膚艱糧) 更多