ALK-positive anaplastic large cell lymphoma

—Phase 1 study shows lorlatinib holds significant promise in the treatment of newly diagnosed ALK-driven high-risk neuroblastoma and has led to a major amendment in a phase 3 pediatric neuroblastoma trial— PHILADELPHIA, April 3, 2023 /PRNewswire/ -- In a significant step for the treatment of neuroblastoma, an international group of researchers led by Children's Hospital of Philadelphia (CHOP), Winship Cancer Institute of Emory University and the New Approaches to Neuroblastoma Therapy (NANT) Consortium has shown that the targeted therapy lorlatinib is safe and effective in treating high-risk neuroblastoma. The findings, published today in Nature Medicine, have led to a major amendment in a phase 3 Children's Oncology Group (COG) clinical trial, which has incorporated lorlatinib for newly diagnosed ALK-driven high-risk neuroblastoma, as well as a planned amendment to the European phase 3 trial in collaboration with the International Society of Paediatric Oncology European Neuroblastoma (SIOPEN). "The results of this study are exciting for patients with high-risk neuroblastoma whose tumors have a genetic alteration in the ALK gene and who have lacked effective targeted treatment options for this often lethal cancer," said senior study author Yael P. Mossé, MD, Professor of Pediatrics in the Cancer Center at Children's Hospital of Philadelphia (CHOP). "This study is the culmination of decades of work that began at CHOP with our initial discovery of ALK mutations in neuroblastoma in 2008. The difficulties we experienced in targeting ALK with crizotinib in neuroblastoma motivated us to find a more potent ALK inhibitor. We started testing lorlatinib in the lab in 2013 and, as a result of this clinical trial, lorlatinib has now moved upfront in a pivotal COG phase 3 trial, which will hopefully support eventual FDA approval of this treatment. This serves as a paramount example across all pediatric cancers of forward and reverse translation, where we learn from the science and from our patients and make decisions in real-time to fast-track development of new agents when there is potential for substantive impact." "The profound clinical responses seen in this trial, in a highly therapy-resistant, relapsed pediatric cancer population, allows us to now offer lorlatinib into frontline care for newly diagnosed patients with ALK mutated or amplified neuroblastoma, a population known to have inferior survival with standard-of-care, high-risk therapy," said the study's first author and co-chair of the trial Kelly Goldsmith, MD, Co-Leader of the Discovery & Developmental Therapeutics Program at Winship Cancer Institute of Emory University, Director of the Neuroblastoma/MIBG Therapy Program at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and associate professor of pediatrics at Emory University School of Medicine. "This trial will truly change the paradigm of clinical care and improve outcomes for our neuroblastoma patients." Neuroblastoma is an aggressive pediatric cancer that develops from early nerve cells, often appearing as a solid tumor in the chest or abdomen. The disease accounts for up to 10% of childhood cancer deaths, and survival rates are low – less than 50% of patients with the disease survive, and there is still no known curative therapy for patients who suffer a relapse, despite recent improvements in our understanding of this disease and the development of new treatment options. A notoriously challenging disease to cure, neuroblastoma is characterized by a variety of types and subtypes caused by separate and interacting gene mutations, which only adds to the complexity in devising rational and effective therapies. A Crucial Discovery In 2008, Dr. Mossé and colleagues discovered that the anaplastic lymphoma kinase (ALK) gene causes most cases of rare, inherited neuroblastoma. Since then, she and colleagues from around the world have investigated how mutations in the ALK gene lead to different types of nonhereditary neuroblastoma. Subsequent research has showed that abnormal ALK changes drive approximately 20% of newly diagnosed high-risk neuroblastoma and that this frequency is substantially higher among relapsed patients. Based on Dr. Mossé's discovery, in 2009 COG launched a clinical trial for children with neuroblastoma that repurposed crizotinib, an ALK inhibitor that was already approved by the FDA to treat adults with a subtype of lung cancer caused by abnormalities in the ALK gene. This pivotal phase 1/2 trial led to the FDA approval of crizotinib for pediatric patients with relapsed/refractory ALK+ anaplastic large cell lymphoma and for pediatric patients with ALK+ unresectable/relapsed inflammatory myofibroblastic tumors. Next-Generation Treatment However, although crizotinib demonstrated impressive response rates in other ALK-driven cancers, data from the phase 2 COG trial showed that children with neuroblastoma had a response rate of only about 15%, underscoring the need for a next-generation ALK inhibitor that would be more effective. After screening numerous anti-ALK agents, the researchers discovered in preclinical tests that lorlatinib, an ALK and ROS-1 inhibitor, surpassed results seen with crizotinib. Leveraging that data, the researchers were able to test the safety, tolerability, and anti-tumor activity of lorlatinib in a first-in-child NANT Consortium Phase 1 trial in children, adolescents and adults with ALK-driven refractory/relapsed neuroblastoma. New Approaches Show Promise In the phase 1 NANT trial, researchers found that lorlatinib given alone or in combination with chemotherapy was safe and tolerable in pediatric, adolescent, and adult patients with relapsed/refractory ALK-driven neuroblastoma. Lorlatinib demonstrated clinical activity across patients of all ages harboring the three neuroblastoma-specific hotspot ALK mutations, including patients who had previously received other ALK inhibitors. Approximately 30% of patients under the age of 18 responded to the drug, and approximately 67% of patients over 18 responded. Patients under the age of 18 had a better response in combination with chemotherapy, with 63% of patients responding to the combined treatment. The researchers noted that younger patients treated with lorlatinib alone – particularly those with amplification of an oncogene called MYCN – had fewer responses compared to older patients. They suspect this could reflect the heterogeneity within the tumor in these patients and indicate that for patients with MYCN mutations, lorlatinib alone will be insufficient, but holds promise when given in combination with chemotherapy. Swiftly moving this drug upfront for the subset of patients with ALK alterations provides an opportunity to go after a key driver of this disease to prevent relapse. The safety profile of lorlatinib across all ages was similar in scope and grade to those reported in studies examining lorlatinib in non-small cell lung cancer. The neuroblastoma patients using lorlatinib also experienced weight gain and increased circulating lipids, but those were manageable with supportive care and diet management. In addition to the NANT sites in the U.S. and Canada, the study also included sites in the U.K. and France. The trial was funded by the National Cancer Institute (grant P01CA217959) and Pfizer, Inc. Additional support came from NCI grants R01CA140198 and R35CA220500, as well as Solving Kids Cancer US/UK, the St. Baldrick's Foundation, V Foundation for Cancer Research, Alex's Lemonade Stand Foundation, Children's Neuroblastoma Cancer Foundation, The Band of Parents, the EVAN Foundation, Wade's Army, Ronan Thompson Foundation, the Catherine Elizabeth Blair Memorial Foundation, and Cookies for Kids Cancer. Goldsmith et al. "Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase I trial results," Nature Medicine, April 3, 2023, DOI: 10.1038/s41591-023-02297-5 About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . About Winship Cancer Institute of Emory University Winship Cancer Institute of Emory University is dedicated to discovering cures for cancer and inspiring hope. As Georgia's only National Cancer Institute-designated Comprehensive Cancer Center, Winship researches, teaches, disseminates and provides novel and highly effective ways to prevent, detect, diagnose, treat and survive cancer. For more information, visit winshipcancer.emory.edu. SOURCE Children's Hospital of Philadelphia

据 Insight 数据库 统计，本周（6 月 20 日 - 6 月 25 日）从全球维度来看共有 47 款新药（含类似药及改良新）研发进度推进到了新的阶段，包括 5 款新申报上市，3 款新获批上市；早期新药项目中 13 款首次启动临床，17 款首次申报临床。而国内企业创新药动态爆发增长，逐渐走出疫情所带来的负面影响，本周有 46 款药物进入新的研发阶段。Insight 本周将分别摘取国内外重要新药项目进展作介绍（附列表）。文章篇幅较长，可选择性阅读。国内创新药进展本周国内共 55 款新药进展到了新的阶段，其中国内企业参与的有 46 款。具体阶段而言，包括 3 款获批上市、4 款申报上市、2 款首次启动 III 期临床、15 款首次启动临床、21 款首次申报临床。国内创新药周进度   4 款新药递交上市申请本周国内申报上市新药一览来自：Insight 数据库  （http://db.dxy.cn/v5/home/）药品名称：TQ-B3101企业名称：正大天晴TQ-B3101 是一款 ALK/MET/ROS1 抑制剂，6 月 23 日，该药上市申请获 CDE 受理。>>点此订阅受理号，第一时间获取审评动态据 Insight 数据库 显示，该药首次临床申报在 2015 年 10 月，迄今已经启动了 6 项临床试验，其中包括 3 项 II 期临床，分别针对 ROS1 阳性非小细胞肺癌、ALK 阳性复发/难治性间变性大细胞淋巴瘤（ALCL）。从临床进展推测，申报上市适应症大概率为：ROS1 阳性非小细胞肺癌。TQ-B3101 开发历程概览来自：Insight 数据库  （http://db.dxy.cn/v5/home/）正大天晴在 2022 ELCC 上公布了针对 ROS1 融合阳性晚期 NSCLC 患者的 2 期临床试验（CTR20191078）数据。该研究由陆舜教授和潘宏铭教授担任主要 PI，结果显示，独立评审委员会（IRC）评估的 ORR 为 78.4%（95%CI, 69.6-85.6），mPFS 为 15.6 个月（95%CI, 10.2-27.0），mDoR 为 20.3 个月（95%CI, 11.0-26.1）。详见下图：TQ-B3101 临床试验结果（Insight）来自：Insight 数据库  临床试验结果模块（http://db.dxy.cn/v5/home/）* Insight 数据库即将在 6 月 30 日上线「临床试验结果」模块，提供丰富的筛选检索项、表格+可视化两种数据展示形式，并与数据库全球新药模块打通，轻松掌握新药全生命周期数据，敬请期待~值得一提的是，正大天晴在 5 月末刚刚申报了另一款 1 类新药 TQ-B3139，针对 ALK 阳性 NSCLC。Insight 数据库 显示，该企业目前有 CDK4/6 抑制剂 TQB3616、三代 EGFR 抑制剂 FHND9041、PD-L1 单抗 TQB2450 这 3 款新药处于 III 期临床，上市申报在即。药品名称：纳乐舒单抗企业名称：上海津曼特生物6 月 22 日，CDE 官网显示，石药集团子公司津曼特的 1 类新药「纳乐舒单抗注射液」申报上市获受理（受理号>>CXSS2200061），根据企业公告，该产品即为 RANKL 单抗 JMT103。据Insight 数据库 显示，JMT103 最早于 2016 年 8 月申报临床，除骨巨细胞瘤外，还有多项适应症处于临床开发当中，包括肿瘤骨转移、骨质疏松症、骨恶性肿瘤高钙血症等。JMT103 全球研发进度概览来自：Insight 数据库 （http://db.dxy.cn/v5/home/）JMT103 是新一代创新型全人源抗 RANKL（IgG4）单克隆抗体，可通过抑制多核破骨细胞的生成从而阻断多核破骨细胞介导的骨吸收。今年 3 月，石药宣布 JMT103 在治疗不可切除或手术困难的骨巨细胞瘤的关键临床试验中达到预设终点。JMT103 的 2 期单臂关键注册临床研究（JMT103CN03 ）共纳入了 139 名骨巨细胞瘤受试者，结果显示，JMT103 肿瘤反应率高达 93.5%，起效时间较快，且治疗后提高了可以手术切除的骨巨细胞瘤患者比例；此外，骨巨细胞瘤患者疼痛程度得到缓解，生活质量得到改善。JMT103CN03 试验详情来自：Insight 数据库 （http://db.dxy.cn/v5/home/）目前国内 RANKL 单抗多为地舒单抗及其生物类似药，创新药之中，纳乐舒单抗为国产首款申报上市。   3 款新药获批上市本周国内 3 款改良新药获批上市，包括两款来自于齐鲁制药的口溶膜制剂；此外，信达生物 PD-1 单抗信迪利单抗的两大一线适应症也在周一和周五分别获批上市。本周国内获批上市新药一览来自：Insight 数据库  （http://db.dxy.cn/v5/home/）药品名称：美金刚口溶膜、阿立哌唑口溶膜企业名称：齐鲁制药本周五，齐鲁制药的两款改良型新药美金刚口溶膜、阿立哌唑口溶膜同时获批上市，均为国内首款。美金刚是一款阿尔茨海默病治疗药物，属于非竞争性 NMDA 受体拮抗剂，通过抑制 NMDA 受体的过度激活以减少兴奋性毒性、保护神经元，同时不影响认知所需要的 NMDA 受体的生理性活化。目前据 Insight 数据库 显示，除口溶膜外国内美金刚在研剂型包括片剂（53）、胶囊剂（10）、口崩片（4）、缓释/控释胶囊（18）、颗粒剂（1）、口服液体制剂（12）。其中口崩片、颗粒剂尚无获批。阿立哌唑是一款抗精神病用药，全球范围内已获批的适应症包括精神分裂症、急性躁狂、双相障碍及相关激越症状等。据 Insight 数据库 显示，除口溶膜之外，国内阿立哌唑在研剂型包括片剂（27）、胶囊剂（5）、口崩片（13）、口服液体制剂（10）、注射剂（2）、注射用微球（1）。其中注射剂尚无企业获批上市。口溶膜是一种新型口服制剂，是药物与适宜的成膜材料加工制成的膜状制剂，放入口中即粘在给药部位，不易吐出，快速分散，可减少患者不配合服药的现象；对于全身作用的药物来说，活性物质可以经口腔黏膜直接吸收，避免首过效应。在国内仿制药竞争激烈叠加集采的情况下，探索更适合患者的改良型新药或许是个不错的选择。齐鲁是国内口溶膜领先企业，且更多专注于神经系统药物，本次获批的两款药物同属于这一领域。这部分患者尤其需要依从性更好的给药方式。据 Insight 数据库 显示，齐鲁已经开发了多款国内首款口溶膜剂，以满足患者尚未解决的治疗需求。目前，齐鲁已有 9 个口溶膜项目开发，其中 5 款已经获批上市，详见下图：齐鲁制药口溶膜剂研发概况来自：Insight 数据库 （http://db.dxy.cn/v5/home/）药品名称：信迪利单抗企业名称：信达生物本周，信迪利单抗获批两项新适应症：（1）联合化疗一线治疗不可切除的局部晚期、复发性或转移性食管鳞癌；（2）联合化疗一线治疗不可切除的局部晚期、复发性或转移性胃或胃食管交界处腺癌。这是信迪利单抗获批的第 5 和第 6 项新适应症。这两项适应症均在 6 月 30 日获得批准，意味着将在今年的医保谈判中亮相，有望在明年初就正式进入医保支付范围。信迪利单抗一线食管鳞癌适应症和一线胃癌适应症分别基于 III 期临床试验 ORIENT-15 研究和 ORIENT-16 研究的数据。据 Insight 数据库 显示，这两项临床数据均在 2021 ESMO 大会上公布，详细数据如下：ORIENT-15 临床试验结果（Insight）ORIENT-16 临床试验结果（Insight）来自：Insight 数据库 临床试验结果模块（http://db.dxy.cn/v5/home/）* Insight 数据库即将在 6 月底上线「临床试验结果」模块，提供丰富的筛选检索项、表格+可视化两种数据展示形式，并与数据库全球新药模块打通，轻松掌握新药全生命周期数据，敬请期待~此外值得一提的是，信迪利单抗是目前唯一获批一线治疗胃癌的国产 PD-1 单抗，有望使国内患者迎来首款医保支付范围内的胃癌免疫疗法。不过同样在本周，百济神州的 PD-1 单抗替雷利珠单抗也申报了一线胃癌适应症。   15 款新药启动临床本周国内共 15 款新药首次启动临床，包括 11 款创新药、2 款改良新、2 款生物类似药。企业方面，本周 MVP 为石药集团，新药、改良新、生物类似药各有 1 款首次公示启动临床。篇幅有限，此处不再赘述，更多新药信息可点击>> Insight 数据库全球新药模块 直达查询。本周国内启动临床新药一览来自：Insight 数据库  （http://db.dxy.cn/v5/home/）境外创新药进展本周境外共有 8 款新药（含改良新）研发进度推进到新阶段。除此之外，新适应症的申报获批也颇受关注，包括第一三共/阿斯利康 Enhertu、百时美施贵宝 CAR-T 疗法、艾伯维 CGRP 拮抗剂等。本周境外发生进展的新药来自：Insight 数据库  （http://db.dxy.cn/v5/home/）药品名称：艾拉司群企业名称：Menarini Group/Radius Health近期，Menarini Group 与 Radius Health 联合宣布已向美国 FDA 递交口服选择性雌激素受体降解剂（SERD）elacestrant 的新药上市申请（NDA），用于治疗 ER+/HER2- 晚期或转移性乳腺癌患者。这项申请基于 III 期临床试验 EMERALD 研究的积极数据。两家公司还表示，计划于 2022 年下半年向欧盟 EMA 递交上市许可申请（MAA）。Elacestrant 即艾拉司群，据 Insight 数据库 显示，艾拉司群最早由卫材研发，而后与 Menarini 和 Radius 达成合作。艾拉司群权益关系图来自：Insight 数据库  （http://db.dxy.cn/v5/home/）艾拉司群是全球首个在关键注册临床中获得获得积极顶线结果的口服 SERD 类药物。EMERALD 研究是一项随机、开放标签、活性对照的 III 期临床试验，评估 elacestrant 作为二线或三线单药疗法治疗 ER+/HER2- 晚期或转移性乳腺癌的疗效和安全性。该项研究共纳入了 477 例患者，试验的主要终点为总体病患与带有 ESR1 基因突变病患的无进展生存期（PFS），而次要终点则是总生存期（OS）、客观缓解率（ORR）与缓解持续时间（DOR）。其临床结果详见下图：EMERALD 研究数据（Insight）来自：Insight 数据库  （http://db.dxy.cn/v5/home/）药品名称：Breyanzi企业名称：百时美施贵宝本周，百时美施贵宝的 CD19 靶向 CAR-T 疗法 Breyanzi 连续达到两项里程碑，新适应症在欧洲申报上市获受理，并在美国获批上市。6 月 20 日，BMS 宣布欧洲 EMA 已经受理 CD19 靶向 CAR-T 疗法 Breyanzi（研发代号：JCAR017）二线治疗，用于一线治疗失败后复发或难治性大 B 细胞淋巴瘤（LBCL）成人患者。6 月 25 日，这项适应症获 FDA 批准在美国上市。Breyanzi 是首个在二线治疗中取得成功的 CAR-T 疗法。在 2021 年 6 月 10 日，BMS 宣布随机、全球多中心 III 期临床试验 TRANSFORM 研究（NCT03575351）达到了主要终点和关键次要终点，相较于标准疗法具有统计学意义的改善，拉开了细胞疗法向更前线治疗进军的序幕。在欧美的申报正是基于该项研究。在 2021 年末的 ASH 大会上，BMS 以口头汇报的形式公布了 TRANSFORM 研究的结果。该项研究共纳入 184 名患者，1:1 随机接受 Breyanzi 或标准疗法。数据详见下图：TRANSFORM 研究在 2021 ASH 上发布的最新数据（Insight）来自：Insight 数据库 临床试验结果模块（http://db.dxy.cn/v5/home/）目前据 Insight 数据库 显示，全球已有 7 款 CAR-T 疗法获批上市。其中，BMS、吉利德、诺华这三家已经向二线疗法发起冲击。全球已获批 CAR-T 疗法适应症及上市地区来自：Insight 数据库 全球新药模块（http://db.dxy.cn/v5/home/）尽管 Breyanzi 率先取得临床成功，但吉利德在 CAR-T 疗法的前线拓展上领先一步。2021 年 6 月 28 日，也就是 BMS 公布临床成功当月，吉利德也官宣了 Yescarta 二线 3 期临床 ZUMA-7 研究的积极结果，并在同年 10 月率先申报上市，今年 4 月初获批。相较于 TRANSFORM 研究，ZUMA-7 研究是首个、同时规模最大的 CAR-T 细胞疗法二线治疗 R/R LBCL 的 3 期随机研究，在全球 77 个中心招募了 359 名患者。另外，作为同靶点同适应症的 CAR-T 疗法，Yescarta 和 Breyanzi 也是直接竞争关系。另一家开发二线适应症的企业是诺华，然而遗憾遭遇失败。2021 年 8 月，诺华宣布 Kymriah 折戟二线侵袭性 B 细胞非霍奇金淋巴瘤（NHL），III 期临床 BELINDA 研究最终未能达到无事件生存（EFS，Event Free Survival）的主要终点。药品名称：Enhertu（Trastuzumab deruxtecan，DS-8201）企业名称：第一三共/阿斯利康6 月 22 日，第一三共宣布欧盟 EMA 已受理 HER2 ADC 新药 trastuzumab deruxtecan（DS-8201，T-DXd，Enhertu®）的新适应症上市申请（Type II Variation application），针对既往接受过至少一次系统治疗后进展或辅助治疗后六个月内复发的 HER2 低表达（IHC 1+ 或 IHC 2+/ISH-）乳腺癌患者。Enhertu 是第一三共与阿斯利康联合开发的 Best-in-class HER2 ADC。在 2022 ASCO 全体大会上，第一三共公布了针对 HER2 低表达乳腺癌的 III 期临床试验 DESTINY-Breast04 研究数据并同步发表于 NEJM，引起轰动。本周这一适应症终于申报上市。DB-04 临床数据来自：Insight 数据库 （http://db.dxy.cn/v5/home/）据 Insight 数据库 显示，第一三共已经针对 Enhertu 构建了治疗版图，覆盖到乳腺癌领域 HER2 阳性群体及 HER2 低表达群体的各线治疗，逐渐取代既往标准疗法，实现 HER2 靶向治疗的制霸。在乳腺癌之后，第一三共还将探索 Enhertu 在胃癌（GC）、非小细胞肺癌（NSCLC）、结直肠癌（CRC）中的疗效。Enhertu 适应症开发甘特图（*仅统计 II 期临床及以上）来自：Insight 数据库 （http://db.dxy.cn/v5/home/）免责声明：本文仅作消息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：加一PR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn点击卡片进入 Insight 小程序药品申报、临床、上市、一致性评价…随时随地查！↓↓ 点击解锁更多新功能

6 月 23 日，CDE 官网显示，正大天晴 1 类新药 TQ-B3101 申报上市。这是一款 ALK/MET/ROS1 抑制剂，根据临床进展推测，这项适应症大概率为：ROS1 融合阳性晚期 NSCLC。点此订阅受理号，第一时间获取审评动态来自：CDE 官网今年 5 月 20 日，正大天晴刚刚申报了另一款 c-Met/ALK/ROS 多靶点酪氨酸激酶抑制剂 TQ-B3139（CT-1139），用于 ALK 阳性 NSCLC（>>点此查看受理号）。仅仅相隔一个月，TQ-B3101 又申报上市，看来天晴的新药开发已经进入爆发期，成果即将兑现，支撑其新药营收不断提高，逐渐抵消仿制药集采影响，实现创新转型。TQ-B3101 和 TQ-B3139 靶点相似，其开发路线又有差异化。前者核心发力方向在 ROS1 阳性实体瘤，后者则偏重于对 ALK 阳性患者群体的治疗。两款创新药的首次临床申报均始于 2015 年，随后双线推进。正大天晴 ALK 靶点创新药来自：Insight 数据库 （http://db.dxy.cn/v5/home/）据 Insight 数据库 显示，TQ-B3101 目前已经启动了 6 项临床试验，其中包括 3 项 II 期临床，分别针对 ROS1 阳性非小细胞肺癌、ALK 阳性复发/难治性间变性大细胞淋巴瘤（ALCL）。TQ-B3101 开发历程概览来自：Insight 数据库  （http://db.dxy.cn/v5/home/）目前，TQ-B3101 的 I 期临床数据和针对 ROS1 阳性 NSCLC 的 II 期临床数据已经公布：TQ-B3101 临床试验结果概览（Insight 数据库）来自：Insight 数据库  临床试验结果模块（http://db.dxy.cn/v5/home/）* Insight 数据库即将在 6 月 30 日上线「临床试验结果」模块，提供丰富的筛选检索项、表格+可视化两种数据展示形式，并与数据库全球新药模块打通，轻松掌握新药全生命周期数据，敬请期待~其中，针对 ROS1 融合阳性晚期 NSCLC 患者的 2 期临床试验（CTR20191078）由陆舜教授和潘宏铭教授担任主要 PI。结果显示，独立评审委员会（IRC）评估的 ORR 为 78.4%（95%CI, 69.6-85.6），mPFS 为 15.6 个月（95%CI, 10.2-27.0），mDoR 为 20.3 个月（95%CI, 11.0-26.1）。详见下图：TQ-B3101 临床试验结果（Insight）来自：Insight 数据库  临床试验结果模块（http://db.dxy.cn/v5/home/）上个月申报上市的 TQ-B3139（CT-1139）则由正大天晴与首药控股联合开发。首药控股负责化合物分子的设计与优化，经过验证的临床前候选化合物转交天晴进行临床阶段开发，双方共同享有知识产权。根据 Insight 数据库，TQ-B3139 进展最快的 III 期临床在 2019 年就已经启动，旨在比较该药与克唑替尼治疗 ALK 阳性晚期 NSCLC 的疗效和安全性；而 II 期临床则针对两项适应症：克唑替尼耐药后的 ALK 阳性晚期 NSCLC，以及 MET 基因异常 NSCLC。除肺癌之外，TQ-B3139 还有两项不同癌种适应症获批临床，分别为弥散性大 B 细胞淋巴瘤和神经母细胞瘤，不过暂未启动临床。TQ-B3139 各适应症临床试验进展来自：Insight 数据库 （http://db.dxy.cn/v5/home/）在 2020 ASCO 大会上，正大天晴曾发表一项 TQ-B3139 的 1 期临床数据（NCT03099330，摘要号：9585）。该研究纳入 63 例至少一种抗肿瘤系统治疗后失败的晚期 NSCLC 患者，其中 59 例为 ALK 阳性，4 例为 ROS1 阳性。从疗效数据来看，截至 2020 年 1 月 23 日，所有患者的中位 PFS 为 12.1 个月（95％CI 8.5-15.6），患者总体 ORR 为 73%（46/63），DCR 为 85.7%（54/63）。ALK TKI 初治和耐药患者的 ORR 分别为 78.7％（37/47）和 56.3％（9/16）；在基线有可测量病灶的脑转移患者中，脑病灶的 ORR 为 80.0％（8/10）。据 Insight 数据库 显示，正大天晴的新药管线已经逐渐进入收获期。不仅后期管线的报批迅速推进着，早期管线也逐渐有了更深厚的积累，申报临床和启动临床的项目都在 2021 年出现了显著高峰。投资科兴获得的丰厚收益，也使其拥有更充裕的资金以支持创新，形成良性循环。正大天晴国内创新药项目趋势来自：Insight 数据库 （http://db.dxy.cn/v5/home/）在近期申报的两款新药之外，天晴还另有 2 个新药处于 III 期临床，分别为 CDK4/6 抑制剂 TQB3616、三代 EGFR 抑制剂 FHND9041；另有 8 个新药处于 II 期临床，42 个新药处于 I 期临床。点击以下卡片进入 Insight 小程序一览「正大天晴」所有在研创新药项目免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：加一PR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn点击阅读原文免费试用 Insight 数据库