A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants with EGFR Alterations or Fusions Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration with PK-triggered Expansion Cohort

This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma. BDTX-1535 was designed to block a growth signal important to some cancers. BDTX-1535 is being tested in this study to see if it can be given safely to people who have tumors that can be dependent on that growth signal because of changes in a protein called EGFR. These gene changes are called amplifications, mutations, fusions or alterations and are found only in the tumors.

开始日期2023-10-18

申办/合作机构

St. Joseph's Hospital

[+1]

NCT05256290

/ Recruiting临床1/2期

A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer

BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of BDTX-1535. The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma (GBM) expressing EGFR alterations (Phase 1 only). All patients will self-administer BDTX-1535 monotherapy by mouth in 21-day cycles.
Phase 1 enrollment is now complete. Phase 2 is currently enrolling.

开始日期2022-03-31

申办/合作机构

Black Diamond Therapeutics, Inc.

100 项与 BDTX-1535 相关的临床结果

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100 项与 BDTX-1535 相关的转化医学

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100 项与 BDTX-1535 相关的专利（医药）

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项与 BDTX-1535 相关的文献（医药）

2024-11-01·Translational Cancer Research

Targeting C797S mutations and beyond in non-small cell lung cancer—a mini-review

Review

作者: Fenchel, Klaus ; Dempke, Wolfram C M

Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases and has a high mortality worldwide, however, targeting common epidermal growth-factor receptor (EGFR) alterations (i.e., del19, L858R) has provided a paradigm shift in the treatment of NSCLC. Uncommon EGFR mutations, however, show variable efficacy to EGFR-targeted drugs depending on the molecular alterations within exons 18-21 which underlying biological mechanism are far from being clear. The substitution mutations of G719X in exon 18, L861Q in exon 21, S768I in exon 20, and exon 20 insertions are the most frequent mutations among the uncommon mutations. The development of fourth-generation EGFR-tyrosine kinase inhibitor (TKIs) has gained increased interest as these drugs are able to inhibit resistance mutations (e.g., C797S) often detected in NSCLC patients' resistance to third-generation EGFR TKIs. BDTX-1535 is an orally bioavailable, brain-penetrating, mutation-selective, irreversible EGFR inhibitor with significant antitumour activity in NSCLCs and glioblastomas (phase I/II trials ongoing). It is a fourth-generation EGFR inhibitor that was found to overcome resistance to osimertinib in preclinical models and has shown promising activity in NSCLC patients harbouring C797S mutations. In experimental models BDTX-1535 was found to inhibit all common EGFR mutations and more than 50 of uncommon mutations including T790M, C797S, L718X, E709X, S784F, V834L and A289V, however, exon 20 insertions are inhibited to a much lesser extent. In addition, mutations in the extracellular domain of the EGF receptor (e.g., EGFRvII, III, IV) can be blocked as well. It should be noted that in up to 50% of all NSCLC patients who progress following osimertinib or other EGFR TKI therapy no underlying resistance mechanism can be identified suggesting that non-mutational signal transduction pathways may also be operative, and intratumoural heterogeneity has been found to be a major contributor to resistance and it consists of three main mechanisms: (I) drug-tolerant persister (DTP) cells, (II) chromosomal instability, and (III) extrachromosomal extracellular DNA (ecDNA) (seen in over 50% of NSCLCs) suggesting that novel EGFR TKIs will include many challenges in sufficiently targeting on-target resistance mechanisms. The development of novel drugs that can overcome TKI resistance in NSCLC patients harbouring the C797S mutation and beyond is, therefore, eagerly warranted.

2021-12-01·Cancer discovery1区 · 医学

BDTX-1535 Goes after Osimertinib Resistance

1区 · 医学

Article

Abstract:

According to a preclinical report, the investigational tyrosine kinase inhibitor BDTX-1535 may mitigate resistance to osimertinib, the standard of care for EGFR-mutant non–small cell lung cancer. It could also potentially treat central nervous system metastases, having shown preclinical efficacy in glioblastoma.

项与 BDTX-1535 相关的新闻（医药）

2024-12-23

·CPHI制药在线

EGFR靶点研发，进展到哪一步了？

关注并星标CPHI制药在线表皮生长因子受体（EGFR）是抗肿瘤领域的经典靶点，针对该靶点，目前已有多款药物上市，典型的如EGFR-TKI（EGFR酪氨酸激酶抑制剂），已上市三代药物，第四代呼之欲出。随着耐药现象出现，针对EGFR靶点药物的研发也在不断迭代。如今，该靶点研发进展如何？ EGFR-TKI迭代之战 EGFR是一种跨膜蛋白，具有胞外配体结合区，跨膜区和胞内激酶区三个结构元件。正常生理状态下，EGFR的激活表现为配体依赖型，EGFR与配体结合后，完成二聚化，调动酪氨酸激酶结构域中的关键调节元件，激活下游信号通路，促进细胞的生存、生长和增殖。当EGFR发生突变时，如过表达，细胞表面会出现过量受体，使细胞不受控制地生长和分裂，诱导正常细胞逐渐转化为癌细胞。另外，EGFR突变会导致受体的行为方式发生变化，导致受体持续将表皮生长因子蛋白吸引到细胞表面，这同样可促进异常的细胞生长。目前抗EGFR药物主要包括酪氨酸激酶抑制剂（TKI）和抗EGFR的单克隆抗体（mAb）。小分子TKI 通过与ATP竞争结合EGFR中的酪氨酸激酶结构域，从而抑制EGFR自身磷酸化和下游信号传导。从2002年，吉非替尼作为第一款EGFR-TKI在日本获批上市起，截至目前，市面上已有一代、二代及三代EGFR-TKI上市。一代代表药物有吉非替尼、厄洛替尼、埃克替尼，这些药物与靶点的结合并不牢固，是可逆的。二代代表药物主要有阿法替尼和达克替尼，特点是与 EGFR 靶点的结合是不可逆的，永久性地锁住靶点。第一、二代EGFR-TKI虽然疗效显著，但多数患者都会在1-2年内出现耐药，为了克服耐药性，三代横空出世，其代表药物主要有奥希替尼和阿美替尼。但第三代靶向药也不可避免的会产生耐药，其耐药原因主要为EGFR C797S耐药突变。为了克服耐药性，一部分药企正在研发第四代，其中以BDTX-1535的数据最为亮眼。BDTX-1535由Black Diamond Therapeutics研发，在II期临床试验中，接受每日1次200mg BDTX-1535治疗的EGFR突变型NSCLC患者有42%（8/19）实现了客观缓解。抗EGFR抗体药物与EGFR-TKI作用机制不同，抗EGFR单克隆抗体通过与EGFR的细胞外结构域结合来阻断配体诱导的EGFR酪氨酸激酶活化，从而与配体竞争性结合。目前已上市的抗EGFR单克隆抗体药物包括西妥昔单抗、尼妥珠单抗、帕尼单抗等，不过它们在NSCLC领域并未取得理想效果，研究人员开始将注意力集中到抗EGFR双抗的研发。强生的Rybrevant（amivantamab-vmjw，埃万妥单抗）是一款靶向EGFR和MET的全人源双特异性抗体，已在美国、欧洲和全球其他市场获批作为单一疗法，用于治疗具有EGFR外显子20插入突变（EGFR ex20ins）的局部晚期或转移性NSCLC患者。2024年8月20日，强生再次宣布Rybrevant联合第三代EGFR-TKI Lazcluze（lazertinib，兰泽替尼）获FDA批准，用于一线治疗局部晚期或转移性NSCLC患者，该方案是第一个与奥希替尼相比，显示出更优的无进展生存期（PFS）的无化疗方案。 EGFR ADC 靶向EGFR的ADC产品的开发历时已久。2008年，雅培与Life Science Pharma达成一项合作协议，获得了后者4款靶向EGFR产品的全球开发和商业化许可权益，其中便包括了两款EGFR ADC：ABBV-321（Serclutamab talirine）和ABBV-414（Depatuxizumab mafodotin，ABT-414），这两款药物后来被艾伯维收入囊中，但是研发进展并不顺利，后续相继折戟。目前，布局EGFR ADC赛道的多为国内公司。进度靠前的有乐普生物的维贝柯妥塔单抗（MRG003），这是一款靶向EGFR的ADC药物，目前已在国内申报上市。另外，MRG003与PD-1抑制剂普特利单抗的联合治疗也取得了积极进展。百利天恒和BMS合作的靶向EGFR/HER3的双抗ADC产品BL-B01D1，目前已在六大瘤种中开展了III期研究，包括EGFR突变型和野生型非小细胞肺癌、鼻咽癌、食管鳞癌、三阴性乳腺癌以及HER2-/HR+乳腺癌，尽管当前仅报出部分I期和小II期探索数据，但其大III期的布局迅猛之势让市场充满期待。百力司康开发的靶向EGFR的ADC产品BB-1705，目前处于临床II期阶段。 EGFR Protac 对于EGFR-TKI耐药难题，PROTAC或许是一个好的解决方案。它可以降解整个蛋白，而不仅仅是抑制酶活性，因此EGFR是一个理想的PROTAC靶标。目前海思科的EGFR PROTAC药物HSK40118和贝达药业/C4 Therapeutics的EGFR PROTAC药物CFT8919，分别已获药监局批准开展临床试验，用于治疗不可手术的、携带EGFR突变的晚期NSCLC患者。随着对EGFR及其下游信号通路的不断探索，开启了肿瘤治疗新时代。近些年来，在抗体、ADC、Protac技术发展带动下，该经典靶点越来越受到关注。EGFR赛道，已翻开新的一页。参考来源： 1.Yasheng Zhu, Xiuquan Ye, Hao Shen, Jiaxing Li, Zeyu Cai, Wenjian Min, Yi Hou, Haojie Dong, Yuxing Wu, Liping Wang, Xiao Wang, Yibei Xiao, and Peng Yang, Discovery of Novel Fourth-Generation EGFR Inhibitors to Overcome C797S-Mediated Resistance, J. Med. Chem. 2023, 66, 14633?14652. 2.https://investors.blackdiamondtherapeutics.com/press-releases. 3.Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP. doi.org/10.1021/acs.jmedchem.1c00649. J. Med. Chem.2021, 64, 11, 7839-7852. END 【智药研习社近期直播】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

上市批准申请上市临床2期ASH会议

2024-11-25

·医药魔方

EGFR新药研发：进化无止境

EGFR（表皮生长因子受体）作为经典靶点在肺癌治疗史中的篇章从未完结。“推陈出新，新益求新”是对EGFR新药研发最好的概括。时间拉回至2002年，吉非替尼在日本上市，开启了EGFR-TKI的时代，但这只是故事的开端，往后十几年里，药物研发者都在与EGFR抑制剂诱导的耐药突变进行着你来我往的斗争。这场战事仍在继续，而药物研发者手中的武器也更加多样化——新一代EGFR-TKI、EGFR抗体、EGFR ADC、EGFR PROTAC……陆续走向擂台中央。近期，EGFR 赛道传来了不少好消息，第一个四代EGFR-TKI即将进入III期阶段、第二个EGFR ADC申报上市、第一个可透脑EGFR抑制剂获批上市……EGFR赛道的篇章已经翻开了新的一页。 EGFR-TKI分子进化：遇变则变，遇强则强 EGFR的发现源于Stanley Cohen等人对细胞生长过程的研究。1962年，Stanley Cohen团队发现表皮生长因子（EGF）可以让实验小鼠提前睁开双眼并长出牙齿[1-4]。经过十多年的深入研究后，Stanley Cohen团队再次贡献了里程碑式的成果——EGFR被揭开面纱。在EGFR与癌症的关系被阐明的几十年间，无数科学家前赴后继踏上研发EGFR-TKI的旅程。 EGFR是一种跨膜糖蛋白，其胞外部分由I、II、III、IV四个子结构域组成，其中I和III为EGF等配体与之结合的配体结合结构域，而结构域II参与受体的二聚化；其胞内部分的关键成份为酪氨酸激酶结构域，这个结构域又分为N-lobe、ATP结合位点、激活环状结构和C-lobe四部分，其中ATP结合位点便为前三代EGFR-TKI的结合位点。 EGFR结构域及耐药性突变机制[5] 2002年，吉非替尼作为第一款EGFR-TKI在日本获批上市，但当时基于生物标志物进行肿瘤患者分层治疗的概念还未发展成熟，险些让EGFR这颗明珠蒙尘。7年后，吉非替尼联手伴随诊断开启基于生物标志物的肺癌精准治疗时代，携带EGFR常见突变（L858R/Ex19del）的非小细胞肺癌（NSCLC）患者得以获益。 NSCLC中的EGFR突变[6] 在跨越了患者分层这个关键障碍之后，吉非替尼还没来得及大展拳脚便又遭遇了生涯中的另一道坎——肺癌细胞进化出EGFR T790M耐药性突变躲避伤害。在吉非替尼之后上市的厄洛替尼和埃克替尼，因作用机制相同，均被束缚了拳脚。有数据显示，对吉非替尼和厄洛替尼耐药的NSCLC患者中超过50%存在EGFR T790M耐药性突变[7]。EGFR T790M耐药性突变将EGFR基因20外显子第790位点的苏氨酸（Thr）替换为甲硫氨酸（Met），使得第一代EGFR-TKI在与ATP竞争性结合ATP结合位点的对抗战中败下阵来。从这一刻开始，针对EGFR耐药性突变迭代EGFR-TKI新药分子的拉锯战拉开帷幕。已上市EGFR-TKI汇总 2015年至今，以奥希替尼为代表的三代EGFR-TKI让研发人员在这场战事中占据了上风。它们通过不可逆地结合ATP结合口袋的EGFR C797位点来有效避开EGFR T790M耐药性突变的影响，同时保持对EGFR L858R/Ex19del突变的有效抑制。三代EGFR-TKI的疗效确实显著。奥希替尼相比于吉非替尼和厄洛替尼，可将EGFR突变型NSCLC患者的疾病进展风险降低54%。更为值得一提的是，奥希替尼还在今年9月获得FDA批准用于治疗III期NSCLC患者，这是小分子EGFR抑制剂第一次闯进早期肺癌的治疗阵地。EGFR-TKI的应用潜力再次被放大。但三代EGFR-TKI依然面临着严峻的肿瘤耐药挑战。在经奥希替尼二线治疗后出现耐药的NSCLC患者中，大约10%-26%的患者存在EGFR C797S耐药性突变[8-9]。EGFR C797S耐药性突变将EGFR基因20外显子第797位点的半胱氨酸（Cys）替换为丝氨酸（Ser），阻碍三代EGFR-TKI与ATP结合位点结合。这场对抗之战已然来到第四阶段。针对EGFR C797S耐药性突变的四代EGFR-TKI已在路上。相比于前三代EGFR-TKI，四代EGFR-TKI在作用机制上更加多样化，开始关注针对EGFR变构位点（位于ATP结合位点内部）的开发价值。医药魔方Nextpharma数据库显示，全球已经有20余款四代EGFR-TKI进入临床阶段，有3款药物公布了初步的临床数据，其中以BDTX-1535的数据最为亮眼。在II期研究中，接受每日1次200mg BDTX-1535治疗的EGFR突变型NSCLC患者有42%（8/19）实现了客观缓解。部分在研四代EGFR-TKI 不过，BDTX-1535作用的位置并不是EGFR胞内的变构位点，而是EGFR胞外变构位点，以此影响EGFR的二聚化。除了克服耐药性突变这个核心目标，小分子EGFR抑制剂赛道的其他分支也开始涌现新的进展，特别是在EGFR罕见突变NSCLC和脑转移NSCLC治疗领域。这两类患者群体的规模不容忽视：EGFR罕见突变占总体EGFR突变NSCLC人群的23%-30%，出现脑转移的肺癌患者占到总人数的16%-20%。针对这两类人群的治疗需求，部分EGFR抑制剂正在展现出令人瞩目的治疗潜力。针对罕见突变或具备脑渗透性的EGFR抑制剂伏美替尼是其中的代表。艾力斯医药在WCLC 2024大会上披露的数据显示，携带EGFR PACC突变（占总体EGFR突变12%）的NSCLC患者接受240mg伏美替尼作为一线治疗后，确认的客观缓解率（cORR）高达63.6%，并且中枢神经系统（CNS）转移患者的cORR达到了46.2%[10]。近日获批上市的佐利替尼对伴CNS转移的NSCLC患者有着不错的疗效，助其成功拿下“第一款可用于CNS转移NSCLC的EGFR抑制剂”殊荣，也算是在战况激烈的EGFR-TKI赛道初步完成了突围。针对EGFR 罕见突变有效和具备脑渗透性也是四代EGFR-TKI的迭代方向，这也是在市场竞争中脱颖而出的手段。BDTX-1535率先做出了表率——EGFR PACC突变型NSCLC患者的ORR达到44.4%。不过，精心设计并不意味着100%成功，四代EGFR-TKI还要等待成药性的检验。耐药性困局：另辟他径，围而破之 EGFR-TKI固然高效，但耐药性问题一直悬而未决，而针对一次次的靶点蛋白突变进行分子迭代也让EGFR-TKI新药开发陷入了循环的僵局。毫无疑问，僵局需要被打破。 EGFR抗体、EGFR ADC、EGFR PROTAC都是可能的方向。 EGFR抗体药物早在2004年便实现了“零”的突破，西妥昔单抗在当年获批上市。遗憾的是，西妥昔单抗以及紧跟其后的尼妥珠单抗和帕尼单抗均未能攻克NSCLC的壁垒，但这一领域的探索从未停止。直到2015年，necitumumab获批用于治疗NSCLC才让EGFR抗体药在肺癌治疗领域中的应用突破显现出新的希望。但是，necitumumab能够为NSCLC患者带来的生存获益甚微，无法与EGFR-TKI匹敌。雪上加霜的是，肺癌细胞对EGFR抗体也进化出了耐药特性。从EGFR信号轴的活化机制猜测来看，EGFR抗体表现不佳的原因可能是胞内突变（Ex19Del、Ex20ins和T790M）会导致EGFR无需配体的参与即可发生二聚化[11, 12]，进而激活下游通路，导致与胞外结构域结合的抗体药物收效甚微。从这种观点出发，搭档EGFR-TKI实现胞外胞内双控有可能是EGFR抗体的“救命稻草”。然而，西妥昔单抗+阿法替尼[13-14]和尼妥珠单抗+吉非替尼[15]都没能以此挽尊。EGFR/c-Met双抗amivantamab（埃万妥单抗）倒是借助兰泽替尼在III期研究中打败了奥希替尼单药[16]，并借此成为EGFR L858R/Ex19del突变型NSCLC患者的一线治疗方案，而amivantamab单药目前仅能用于EGFR exon 20ins突变型NSCLC。 II-III期在研EGFR抗体不过，倒也不必对EGFR抗体完全失去信心，持续突破的新技术总能为其找到用武之地。时下热门的ADC技术就是EGFR抗体的另一条出路。ADC药物的优势在于利用抗体端高度靶向肿瘤部位，而后通过释放细胞毒药物实现精准杀伤效果。就这一点而言，EGFR ADC有可能避开EGFR抗体存在的问题。临床在研EGFR ADC 艾伯维是最早行动的玩家，但铩羽而归。2019年，ABBV-414在胶质母细胞瘤III期研究中落败于安慰剂，还未会师NSCLC便中道夭折。在此之后，ABBV-221和ABBV-321两款EGFR ADC继续折戟，艾伯维心灰意冷几欲退出赛道。 ABBV-414失败的第二年，基于西妥昔单抗开发的光免疫疗法Akalux（cetuximab saratolacan）在日本上市，完成EGFR ADC赛道“从0到1”的里程碑。不过，受限于使用上的不便——需要通过激光系统进行局部激活和适应症的狭窄——仅限于头颈癌，再加上疗效平平，这款药物并没有得到广泛应用，也没有在日本以外的国家上市。一直到今年，EGFR ADC赛道才出现新的希望，由乐普生物开发的维贝柯妥塔单抗（MRG003）借II期研究数据提交上市申请。不过，乐普生物为维贝柯妥塔单抗选择的首发适应症是鼻咽癌，而这款药物对EGFR阳性NSCLC的疗效如何还未见揭晓。另一款值得关注的药物是EGFR/HER3双抗ADC伦康依隆妥单抗（BL-B01D1）。这款药物已经在I期研究中初步显露实力。EGFR突变型NSCLC接受其治疗后，ORR达到63.2%（24/38）；EGFR野生型NSCLC接受其治疗后，ORR达到44.0%（22/50）。 EGFR PROTAC是近年来兴起的新赛道，其治疗概念在于通过直接降解EGFR解决多种耐药性突变。相比于局限特定EGFR突变类型的EGFR-TKI，PROTAC在适用性上的确更强，可以为解决EGFR耐药难题提供全新的思路。但PROTAC作为一种前沿技术，其成药性还未得到充分的探索。目前进入临床阶段的EGFR PROTAC也只有零星的几款。临床在研EGFR PROTAC 总结 EGFR赛道的发展历程见证了肺癌治疗格局的风云变幻。首先破茧的EGFR-TKI让肺癌治疗走出传统化疗的局限，走进靶向治疗时代，而后在短短十几年间完成从一代药物到三代药物的更迭，如今四代药物也快看见曙光。再看近几年，EGFR抗体和EGFR ADC逐渐成型，EGFR PROTAC也陆续出现进展，EGFR-TKI的短板正在被一点一点弥补。期待EGFR药物能够在肺癌治疗的地图上继续点亮一片新的领域。 - 上下滑动查看参考资料 - [1] Stanley Cohen—Nobel Laureate for Growth Factor. Mayo Clinic Proceedings. 1999. 74(6):600. [2] Stanley Cohen: awarded Nobel prize in medicine for his discoveries of growth factors. BMJ. 2020. 368:m983. [3] Precocious Newborn Mice and Epidermal Growth Factor: the Work of Stanley Cohen. Journal of Biological Chemistry. 2006. 281(10):e10-e11. [4] Isolation of a Mouse Submaxillary Gland Protein Accelerating Incisor Eruption and Eyelid Opening in the New-born Animal. Journal of Biological Chemistry. 1962. 237(5):1555–1562. [5] Emerging strategies to overcome resistance to third-generation EGFR inhibitors. Journal of Hematology & Oncology. 2022. 15(1):94. [6] From Rarity to Reality: Osimertinib’s Promising Horizon in Treating Uncommon EGFR Mutations in Non–Small Cell Lung Cancer. Clin Cancer Res. 2024. 30 (15): 3128–3136. [7] AZD9291: an irreversible, potent and selective third generation tyrosine kinase inhibitor (TKI) targeting EGFR activating (EGFRm+) and resistance (T790M) mutations in advanced lung adenocarcinoma. AACR 2013. Abstract A109. [8] Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015. 21(6): 560-2. [9] EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors. Clin Cancer Res. 2015. 21(17): 3913-23. [10] FURTHER: A Global, Randomized Study of Firmonertinib at Two Dose Levels in TKI-Naive, Advanced NSCLC with EGFR PACC Mutations. WCLC 2024. PL04.07. [11] Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance. Pharmacol Rep. 2020. 72(4):799-813. [12] Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization. Cancer Res. 2013. 73(22):6770-6779. [13] Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403. J Clin Oncol. 2020. 38(34):4076-4085. [14] First-Line Afatinib plus Cetuximab for EGFR-Mutant Non-Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study. Clin Cancer Res. 2021. 27(15):4168-4176. [15] A randomized, phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12-01). Oncotarget. 2017. 8(9):15943-15951. [16] Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024. 391(16):1486-1498. Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

抗体药物偶联物临床3期上市批准蛋白降解靶向嵌合体临床结果

2024-11-05

·investors.blackdiamondtherapeutics.com

Black Diamond Therapeutics Reports Third Quarter 2024 Financial Results and Provides Corporate Update

Announced encouraging initial Phase 2 data of BDTX-1535 in patients with recurrent EGFRm NSCLC with a broad spectrum of classical, non-classical, and C797S resistance mutations in September 2024 Presented real-world treatment practices and patient outcomes in newly diagnosed NSCLC patients with non-classical EGFR mutations at the 2024 ESMO Congress Clinical updates of BDTX-1535 in EGFRm NSCLC and regulatory feedback expected in Q1 2025 Cash, cash equivalents, and investments of $112.7 million as of September 30, 2024; expected to be sufficient to fund operations into Q2 of 2026 CAMBRIDGE, Mass., Nov. 05, 2024 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, today reported financial results for the third quarter ended September 30, 2024, and provided a corporate update. “We are focused on the advancement of BDTX-1535 for the treatment of patients with EGFRm NSCLC and look forward to providing clinical updates on our Phase 2 trial for both newly diagnosed patients and patients with relapsed/refractory EGFRm NSCLC in the first quarter of 2025,” said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. “We also look forward to sharing feedback on a registrational path in relapsed/refractory EGFRm NSCLC following a meeting planned with the FDA in the first quarter of 2025.” Recent Developments & Upcoming Milestones: BDTX-1535: In September 2024, Black Diamond announced initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor (EGFR) mutant (EGFRm) non-small cell lung cancer (NSCLC). The 200 mg daily dose of BDTX-1535 was selected for pivotal development, showing robust EGFRm target coverage and a favorable tolerability profile with no new safety signals observed. A preliminary overall response rate (ORR) of 42% was seen in 19 patients with known osimertinib resistance EGFR mutations (either C797S or PACC “P-loop αC-helix compressing” mutations). Encouraging durability was noted with a duration of response (DOR) of approximately eight months or more in the first three patients who achieved a partial response (PR), while 14 of the 19 patients remained on treatment. In September 2024, Black Diamond presented a poster analyzing real-world treatment outcomes for newly diagnosed NSCLC patients with non-classical EGFR mutations (NCMs) at the 2024 European Society for Medical Oncology (ESMO) Congress. The analyses revealed the presence of a broad spectrum of NCMs, including PACC mutations, and allowed association with real-world treatment practices and therapeutic outcomes. Findings further demonstrated that current treatment practices for patients with NCMs are heterogenous: 36% of patients received osimertinib or afatinib and 60% of patients received chemotherapy and/or immunotherapy. In October 2024, the Ivy Brain Tumor Center, which is sponsoring a “window of opportunity” (also known as Phase 0/1 “Trigger”) trial of BDTX-1535 in patients with recurrent high-grade glioma (HGG), presented updated study results demonstrating that BDTX-1535 effectively penetrates rarely accessible regions of glioblastoma and suppresses EGFR signaling in patient tumors at the 19th Meeting of the European Association of Neuro-Oncology. These encouraging data provide rationale for the program’s expansion into newly diagnosed glioblastoma patients with EGFR aberrations. In the first quarter of 2025, Black Diamond expects to disclose initial Phase 2 data in first-line EGFRm NSCLC patients with non-classical mutations as well as updated Phase 2 results in the recurrent EGFRm NSCLC setting (NCT05256290) together with an update on a potential registrational path for the recurrent setting. Corporate In October 2024, Black Diamond announced a corporate restructuring plan to prioritize its resources on advancing and optimizing development plans for its lead program BDTX-1535, strengthen operational efficiencies and extend the Company’s expected cash runway into the second quarter of 2026. As part of the restructuring, Black Diamond also deprioritized its Phase 1 RAS/RAF inhibitor, BDTX-4933, and is actively seeking partnerships for the program. Financial Highlights Cash Position: Black Diamond ended the third quarter of 2024 with approximately $112.7 million in cash, cash equivalents, and investments compared to $131.4 million as of December 31, 2023. Net cash used in operations was $11.3 million for the third quarter of 2024 compared to $18.4 million for the third quarter of 2023. Research and Development Expenses: Research and development (R&D) expenses were $12.9 million for the third quarter of 2024, compared to $16.2 million for the same period in 2023. The decrease in R&D expenses was primarily due to workforce efficiencies and reduced spending on early discovery projects. General and Administrative Expenses: General and administrative (G&A) expenses were $5.2 million for the third quarter of 2024, compared to $7.9 million for the same period in 2023. The decrease in G&A expenses was primarily due to a decrease in consulting and other professional fees. Net Loss: Net loss for the third quarter of 2024 was $15.6 million, as compared to $23.0 million for the same period in 2023. Financial Guidance Black Diamond ended the third quarter of 2024 with approximately $112.7 million in cash, cash equivalents and investments which the Company believes is sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second quarter of 2026. About Black Diamond Therapeutics Black Diamond Therapeutics is a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer. The Company’s MasterKey therapies are designed to address a broad spectrum of genetically defined tumors, overcome resistance, minimize wild-type mediated toxicities, and be brain penetrant to treat central nervous system disease. The Company is advancing a Phase 2 NSCLC trial of BDTX-1535, a brain-penetrant fourth-generation EGFR MasterKey inhibitor targeting EGFR-mutant NSCLC and GBM. For more information, please visit www.blackdiamondtherapeutics.com. From time to time, we may use our website or our LinkedIn profile at www.linkedin.com/company/black-diamond-therapeutics to distribute material information. Our financial and other material information is routinely posted to and accessible on the Investors section of our website, available at www.blackdiamondtherapeutics.com. Investors are encouraged to review the Investors section of our website because we may post material information on that site that is not otherwise disseminated by us. Information that is contained in and can be accessed through our website or our LinkedIn page is not incorporated into, and does not form a part of, this press release. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the potential of BDTX-1535 to address the unmet medical need for newly diagnosed NSCLC patients with non-classical EGFR mutations and benefit patients with NSCLC across multiple lines of therapy, the continued development and advancement of BDTX-1535, including the ongoing clinical trials and the timing of clinical updates for BDTX-1535 in patients with NSCLC, the expected timing for regulatory feedback and the disclosure of potential registrational pathways for BDTX-1535 in NSCLC, potential partnership opportunities for BDTX-4933, the expected cost savings from the corporate restructuring plan, the potential future development plans for BDTX-1535 in NSCLC and GBM, and the Company’s expected cash runway. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the United States Securities and Exchange Commission and in its subsequent filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Contact For Investors: investors@bdtx.com For Media: media@bdtx.com

临床结果临床1期财报临床2期

100 项与 BDTX-1535 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
晚期肺非小细胞鳞癌	临床2期	美国	Black Diamond Therapeutics, Inc.	2022-03-31
EGFR阳性非小细胞肺癌	临床2期	美国	Black Diamond Therapeutics, Inc.	2022-03-31
多形性胶质母细胞瘤	临床2期	美国	Black Diamond Therapeutics, Inc.	2022-03-31
转移性非小细胞肺癌	临床2期	美国	Black Diamond Therapeutics, Inc.	2022-03-31
继发性肺恶性肿瘤	临床2期	美国	Black Diamond Therapeutics, Inc.	2022-03-31
非小细胞肺癌	临床2期	美国	Black Diamond Therapeutics, Inc.	-

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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


NCT05256290 (GlobeNewswire) 人工标引	临床2期	复发性非小细胞肺癌二线 EGFR C797S	27	BDTX-1535 200 mg	夢糧鹽獵構鏇網構觸襯(齋鹽壓鏇製糧壓範憲繭) = 鹽網廠鏇窪窪範夢構製繭襯鑰築膚齋積製積齋 (鑰鬱鹽餘獵觸醖構構憲 ) 更多	积极	2024-09-23
NCT05256290 (GlobeNewswire) 人工标引	临床2期	复发性非小细胞肺癌二线 EGFR C797S	27	BDTX-1535 200 mg (either C797S or P-loop alpha-C helix compressing (PACC, a major subset of NCMs))	夢糧鹽獵構鏇網構觸襯(齋鹽壓鏇製糧壓範憲繭) = 築築衊齋糧壓製廠鏇範繭襯鑰築膚齋積製積齋 (鑰鬱鹽餘獵觸醖構構憲 )	积极	2024-09-23
NCT05256290 (BDTX-1535-101, ASCO2024)	临床1期	复发性胶质母细胞瘤 EGFR alterations \| EGFRvIII \| missense mutations	54	BDTX-1535 15mg QD	鹹襯糧繭膚淵廠膚襯憲(淵衊夢繭壓鹹簾壓鑰願) = Gr 3 TRAEs ≥ 10% included rash (19%) reported at 300 or 400 mg QD doses 衊糧淵淵壓膚憲膚鏇餘 (願窪獵蓋蓋衊遞蓋範鏇 ) 更多	积极	2024-05-24
NCT06072586 (Phase 0/1 trigger trial of BDTX-1535, ASCO2024)	早期临床1期	复发性恶性胶质瘤 EGFR alterations \| EGFR fusions	7	BDTX-1535 200 mg	獵膚糧繭築鹽膚願齋選(醖願簾蓋窪構壓選鏇選) = No serious adverse events were observed among patients in the Phase 1 component of the study 齋鹹構蓋膚窪壓餘膚膚 (構窪範廠網艱餘遞糧觸 )	积极	2024-05-24
NCT06072586 (GlobeNewswire) 人工标引	临床1期	复发性胶质母细胞瘤二线	22	BDTX-1535	蓋繭壓蓋積簾遞選蓋廠(鹹積憲鏇憲製範淵積範) = consistent with the EGFR tyrosine kinase inhibitor (TKIs) class of drugs, including primarily Grade 1 and 2 diarrhea and rash 餘鑰選製構壓膚淵糧膚 (艱範積繭製蓋獵膚觸壓 )	积极	2023-12-13
Corporate Publications 人工标引	临床1期	非小细胞肺癌	-	BDTX-1535	觸範艱夢選齋鏇鹹衊鏇(蓋醖壓艱夢廠襯蓋壓獵) = No patients experienced dose limiting toxicity at 15-200 mg QD doses. One of 15 patients treated at the 300 mg QD dose experienced dose limiting diarrhea and 5 of 12 patients at the 400 mg QD dose experienced dose limiting toxicity (diarrhea, 2 patients; rash, stomatitis, fatigue and decreased appetite, 1 patient each). 襯網鹹壓夢壓鏇淵糧艱 (衊鏇築構糧遞齋憲壓齋 ) 更多	积极	2023-06-27