At Big Lung Cancer Meeting, Lights Shine on KRAS, Drug Combos & More


2019-09-11 16:00:00 Xconomy


The treatment landscape for lung cancer has shifted significantly over the past few years, and more changes could be on the way. At the World Conference on Lung Cancer in Barcelona this weekend a number of drug makers trotted out some of their latest advances in immunotherapy, targeted pills, drug combinations, and more. Xconomy rounded up some of the most noteworthy headlines and put them in context below. Spotlight on KRAS Over the past year, a drug called AMG 510, from Amgen (NASDAQ: AMGN) has caused quite a stir, and for good reason. It’s the first drug to inhibit KRAS—a known genetic driver of multiple cancers—to not only make it into human testing, but also to show evidence of an effect in cancer patients. The Amgen drug specifically targets KRAS-G12C, which is implicated in a fraction of cancers that are extremely difficult to treat. Some Wall Street analysts have already placed multi-billion dollar revenue projections on AMG-510 following a Phase 1 update at the American Society of Clinical Oncology’s meeting earlier this year, where the company reported that the drug showed encouraging signs in both lung and colorectal cancers without any serious side effects. About 13 percent of patients with non-small cell lung cancer, the most common form of lung cancer, have a KRAS-G12C mutation. Amgen provided an update to the Phase 1 study this weekend. The drug continued to show promise, but potential limitations as well. At ASCO, five of 10 lung cancer patients and the first three who had been treated on the high dose of AMG-510 all responded, meaning their tumors at least partially shrunk. Amgen now says seven of 13 patients on the high dose, or 54 percent thus far, have responded. Some patients who previously responded have seen their cancer spread. There were still no serious side effects: four of 34 total patients have dropped out of the study, but not because AMG-510. All told, those results “may be perceived as somewhat disappointing by investors,” wrote Jefferies analyst Kennen MacKay, though he added that AMG-510 so far seems superior to other drugs tested for lung cancer patients with KRAS G12C mutations. Shares fell more than 4 percent in pre-market trading. Shares of rival Mirati Therapeutics (NASDAQ: MRTX), which has a rival KRAS-G12C inhibitor, also slumped 6 percent. Amgen will present more data at a medical meeting in Europe later this month and is testing the drug in combination with other medicines, among them immunotherapies. Combo Advances It wasn’t too long ago that chemotherapy was the only option for small cell lung cancer, an aggressive form of the disease linked to smoking. But immunotherapy has changed that: the FDA approved a combination of chemotherapy and the Roche immunotherapy atezolizumab (Tecentriq) in March. Other combinations are on Roche’s heels, and the first challenger comes from AstraZeneca (NYSE: AZN). Last month, AstraZeneca said its immunotherapy durvalumab (Imfinzi) and chemotherapy beat chemo alone in a Phase 3 study, CASPIAN, in newly diagnosed patients with advanced SCLC. On Monday, it provided the details: Durvalumab/chemo cut the risk of death by 27 percent, compared to chemo alone. Patients lived a median of 13 months on the combination versus 10.3 months for chemo. Some 33.9 percent of durvalumab/chemo patients were alive 18 months, versus 24.7 percent of chemo patients. AstraZeneca is discussing the data with regulators, aiming for an approval of its own. Merck (NYSE: MRK) is up next, with Phase 3 data from a study of pembrolizumab (Keytruda) and chemo expected by the end of the year. They’ll be closely watched: Keytruda-chemo is already the standard of care for many patients with non-small cell lung cancer. RET Race A competitive race is on to develop pills to treat non-small cell lung cancer patients with RET mutations. Blueprint Medicines (NASDAQ: BPMC) has already said it plans to file for approval next year of pill pralsetinib, which is being tested in patients with a variety of tumors, among them lung cancer, with RET mutations. On Monday, Eli Lilly (NYSE: LLY) presented results from a 531-patient Phase 3 study called LIBRETTO-001 testing selpercatinib. Lilly acquired the drug (formerly called LOXO-292) when it bought Loxo Oncology for $8 billion in January. The data: 68 percent of patients with RET fusion-positive NSCLC patients who previously got chemotherapy responded to selpercatinib. Those patients responded for a median of 20.3 months. Of 34 RET fusion patients who hadn’t gotten chemotherapy, 85 percent responded. SVB Leerink analyst Andrew Berens said that while the response rates for Lilly’s drug were “slightly higher” than those seen thus far with pralsetinib, “we do not see this delta as meaningful.” “Both drugs are likely to be clinically relevant,” he wrote in a research note. Lilly said it aims to file for approval of rival selpercatinib by the end of the year. The drug is also being tested in patients with medullary thyroid cancer. Shares climbed 3.5 percent in pre-market trading Monday. Blueprint shares ticked down 2.5 percent.
在过去的几年里,肺癌的治疗环境已经发生了显著的变化,而且还可能出现更多的变化。在本周末于巴塞罗那举行的肺癌世界会议上,许多制药商在免疫治疗、靶向药物、药物组合等方面取得了一些最新进展。Xconomic 把一些最值得注意的新闻标题概括起来,并把它们放在下面的上下文中。 KRAS 的聚光灯 在过去的一年中,一种名为 AMG 510的药物,来自安进(Amgen)( NASDAQ : AMGN )已经引起了相当大的轰动,并有充分的理由。这是第一种抑制 KRAS (一种已知的多种癌症的基因驱动因素)的药物,它不仅能使其进入人体测试,还能显示出癌症患者的疗效。安进(Amgen)药物特别针对 KRAS-G12C ,它与极难治疗的一小部分癌症有关。在美国临床肿瘤学会( American Society of Clinical Oncology )今年早些时候召开的会议上,一些华尔街分析师已经对 AMG-510进行了数十亿美元的收入预测。该公司在会上报告称,这种药物在肺癌和结肠癌中都显示出令人鼓舞的迹象,没有任何严重的副作用。约13%的非小细胞肺癌患者(最常见的肺癌形式)有 KRAS-G12C 突变。 安进(Amgen)在这个周末提供了第一阶段研究的更新。该药物继续显示出希望,但也有潜在的局限性。在 ASCO ,接受高剂量 AMG-510治疗的10名肺癌患者中有5名和前3名均有反应,这意味着他们的肿瘤至少部分缩小。安进(Amgen)现在说,在13名高剂量患者中,有7名(到目前为止为54%)已经做出了反应。一些先前作出反应的病人看到他们的癌症扩散。仍然没有严重的副作用:34名患者中有4名已经放弃了研究,但不是因为 AMG-510。 杰富瑞( Jefferies )分析师肯尼•麦凯( Kennen MacKay )写道,总的来说,这些结果“可能被投资者认为有些令人失望”,但他补充称,迄今为止 AMG-510似乎优于其他针对 KRAS G12C 突变肺癌患者的药物。股票在盘前交易中下跌超过4%。竞争对手 Mirati Therapeutics ( NASDAQ : MRTX )的股价也下跌了6%。 本月晚些时候,安进(Amgen)将在欧洲召开的一次医学会议上提供更多的数据,并将与其他药物联合测试该药物,其中包括免疫疗法。 Combo Advances 不久以前,化疗是小细胞肺癌的唯一选择,这是一种与吸烟有关的侵袭性疾病。但是免疫疗法已经改变了这一点: FDA 在3月份批准了联合化疗和罗氏(Roche)免疫疗法联合使用替唑仑单抗( Tecentriq )。其他的组合是罗氏(Roche)公司的脚跟,第一个挑战者来自阿斯利康(AstraZeneca)( NYSE : AZN )。 上个月,阿斯利康(AstraZeneca)称其免疫疗法 durvalumab ( Imfinzi )和化疗在第三阶段研究中击败了化疗, CASPIAN ,在新诊断的晚期 SCLC 患者。周一,它提供了细节:与单独化疗相比, Durvalumab / Chem 将死亡风险降低了27%。患者的平均寿命为13个月,而化疗为10.3个月。约33.9%的杜伐单抗/化疗患者存活了18个月,而化疗患者的这一比例为24.7%。阿斯利康( AstraZeneca )正与监管机构讨论相关数据,以期获得自己的批准。 默克(Merck)公司( NYSE : MRK )将于明年上市,第三阶段数据来自 pembrolizumab (可瑞达(Keytruda))和化学药物的研究,预计年底前完成。他们将受到密切关注: Keytruda-Chemical 已经成为许多非小细胞肺癌患者的护理标准。 RET 种族 一个竞争对手正在开发药物治疗非小细胞肺癌患者的 RET 突变。Blueprint Medicines ( NASDAQ : BPMC )已经表示计划明年申请批准一种药物 prlsetinib ,该药物正在对多种肿瘤患者(其中包括肺癌)进行 RET 突变检测。周一,礼来(Eli Lilly)( NYSE : LLY )公布了一项名为 LIBRETTO-001测试 selperatinib 的531名患者的第三阶段研究结果。今年1月,礼来(Lilly)以80亿美元收购了 Loxo 肿瘤学公司( Loxo Oncology ),从而获得了该药物(以前称为 LOXO-292)。 数据:68%的 RET 融合阳性的非小细胞非小细胞肺癌(NSCLC)患者在接受化疗后对 selperatinib 有反应。这些患者的平均应答时间为20.3个月。在34名未接受化疗的 RET 融合患者中,85%的人做出了反应。 SVB Leelirink 分析师 AndrewBerens 表示,尽管礼来(Lilly)公司的药物的反应速度“略高于”到目前为止与 prlsetinib 的反应,“但我们不认为这个三角洲有意义。” “这两种药物都可能与临床相关,”他在一份研究报告中写道。 礼来(Lilly)表示,计划在今年年底前提交竞争对手 selperatinib 的申请。该药物也正在对髓性甲状腺癌患者进行检测。周一股市开盘前上涨了3.5%。Blueprint 股价下跌2.5%。