Virginia Cancer Specialists PC

癌度医学临床招募资讯微信群（点击） 人表皮生长因子受体2（HER2）是ERBB家族的一个基因，这个基因家族还有一个大名鼎鼎的爱捣乱的分子——EGFR基因。EGFR基因在非小细胞肺腺癌里非常高频地发生突变，50%的肺腺癌患者因为这个基因突变可以选择靶向药治疗。HER2基因在乳腺癌和胃癌里比较常见，HER2发生突变的形式包括HER2基因突变和HER2基因扩增、HER2蛋白高表达。其中HER基因突变和扩增可以使用基因测序技术来确定，HER2蛋白高表达则是通过免疫组化检测。 HER2突变的非小细胞肺癌占所有非小细胞肺癌的2%至5%，这类患者预后不良、脑转移率比较高，治疗难度大。迄今为止，针对HER2阳性的肺癌仅有一种靶向疗法（德曲妥珠单抗）。但是HER2阳性肺癌的治疗需求仍是未被满足。 1、HER2阳性肺癌的特点 非小细胞肺癌的HER2突变大多数发生在特定的位置，其中20号外显子插入突变占主导，最常见的外显子20插入是A775_G776insYVMA，其他的突变形式也存在，但总体频率不是很高。 尽管HER2基因20外显子插入突变对抗体偶联药如德曲妥珠单抗敏感，但是对口服靶向药是耐药的，比如阿法替尼、达克替尼等口服靶向药对这类突变无治疗效果。一些泛靶点的ERBB口服靶向药如吡咯替尼、泼奇替尼对HER2基因20外显子有效，但是也往往伴随相关毒性，比如腹泻和皮疹。这个主要的原因可能是因为是泛靶点，所以不良反应发生率也高。 今天给大家介绍的宗格替尼是一种新型口服靶向药，可以选择性抑制HER2但不抑制EGFR，从而限制了相关毒性。下面就是关于宗格替尼的一个临床试验结果，这也是该药的首次人体、多中心的临床试验结果。 本文参考文献刊例示意图 2、宗格替尼治疗HER2阳性肺癌疗效数据 这是一个代号为Beamion LUNG-1的临床试验，评估每日两次使用宗格替尼（15至150毫克）或每日一次（60至360毫克）给药的效果和安全性。截止2024年5月23日，一共有105名患者接受了治疗，后面推荐的扩展剂量为每日一次120毫克和每日一次240毫克宗格替尼。 宗格替尼治疗HER2阳性肺癌的治疗应答率 如上面的图示，经过确认，所有剂量组30%的可评估疗效患者的肿瘤病灶缩小幅度超过了30%（治疗应答率），中位缓解持续时间为12.7个月。对于之前接受过HER2靶向治疗的肺癌患者有28%的患者病灶缩小超过30%，HER2基因的A775_G776insYVMA突变患者治疗应答率为38%，每日一次接受宗格替尼治疗非小细胞肺癌的中位无进展生存时间是17.2个月。 3、这款药的未来 从上面的疗效数据看，宗格替尼的治疗效果是相当不错的，不管是初治还是经治HER2阳性肺癌都有患者产生治疗应答。上面的临床试验是一期临床试验，这个数据还不能支持这个药物获批，因此这款药会开展二期临床试验以探索好的剂量探索疗效数据，大家可以根据自己的基因检测报告来联系癌度申请入组，以争取获得免费使用这款口服靶向药的机会。 癌度与吉因加启动的“基因检测人人可及”计划里，仅需要3000元就能检测36个基因，大家可以联系癌度或扫描上面的二维码咨询癌度医学顾问，了解基因检测的相关问题。 参考文献： John V. Heymach, MD, PhD, et al., HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study, Journal of Clinical Oncology (2025).  往期推荐  Claudin 18.2系列之一，多种实体肿瘤可受益于这个新靶点的抗癌药，这次点名双抗药QLS31905！ KRAS系列之二：PCM-075联合化疗和贝伐单抗让76%肠癌KRAS突变患者病灶缩小，生存期翻倍！ ALK基因变异亚型、TP53共突变影响了患者靶向药的有效期、生存时间！ 话说肺癌新药，HER2抗体偶联药瑞康曲妥珠单抗刊登《柳叶刀》，73%患者病灶缩小超30%以上！

NEW YORK, Feb. 25, 2025 /PRNewswire/ -- Novita Pharmaceuticals, Inc. ("Novita"), a privately held, clinical-stage pharmaceutical company dedicated to developing novel cancer drugs through its proprietary fascin inhibitor technology, today announced additional results from its Phase 2 study (NCT05023486) evaluating NP-G2-044 in combination with SOC anti-PD-1 therapy in patients with advanced solid tumors resistant to prior anti-PD-1 therapy at the American Association for Cancer Research Immuno-oncology (AACR IO) Annual Meeting. The data was presented in a poster presentation titled "Phase 2 Study of NP-G2-044, a Novel Fascin Inhibitor, in Combination with Anti-PD-1 Therapy in Patients with Solid Tumors Resistant to Prior Anti-PD-1 Therapy." Findings indicate that NP-G2-044 provides a novel therapeutic opportunity when combined with ICIs. "We are very pleased with the findings generated to date in our Phase 2 trial of NP-G2-044 both as a monotherapy and in combination with anti-PD-1 immune checkpoint inhibitors (ICIs) in ICI-resistant patients with advanced and metastatic solid tumors," said Jillian Zhang, Ph.D., President & Chief Scientific Officer of Novita. "The strong safety and durable efficacy we have observed with our first-in-class fascin inhibitor further support the simultaneous inhibition of metastasis and enhancement of cancer immunotherapy as a promising and innovative approach in cancer treatment with broad applications for many solid tumors. We look forward to sharing additional data from the Phase 2 expansion cohort of NP-G2-044 in combination with ICI in the second half of 2025." Among the 45 patients treated with NP-G2-044 as of the last data cutoff (Oct. 2024), 80% had progressed on prior anti-PD-(L)1 therapies. The anti-PD-1 Combination RP2D for NP-G2-044 was 1600 mg QD with 4-week cycles. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), metastasis-free interval (MFI), overall survival (OS), safety, and tolerability. Key highlights include: A Disease Control Rate of 76% (includes patients with Stable Disease and Objective Responses) An ORR of 21% (95% CL 9-38.9%) including 4 patients with Partial Response (PR) and 3 patients with Complete Responses (CR) including Pathologic Complete Response Results indicate durable responses and tumor control in a significant proportion of patients across at least seven cancer types, including cases converted from ICI-non-responsive to ICI-responsive. Long lasting objective responses have been observed. Notable outcomes include a CR in a cervical cancer patient, target lesion CR in an endometrial cancer patient, pathological CRs in a pancreatic cancer patient and a patient with gastroesophageal junction adenocarcinoma and PRs in cutaneous squamous cell carcinoma, non-small cell lung cancer, and cholangiocarcinoma. Seven patients are still on treatments, with the longest duration of 18+ months in an endometrial cancer patient and a patient with pancreatic cancer. An amendment to the study is underway to open additional cohorts. These new cohorts aim to further evaluate the combination of NP-G2-044 with anti-PD-1 therapy across patient populations and solid tumor subtypes, providing a broader understanding of its therapeutic potential. Future analysis will also explore biomarkers for response prediction and mechanisms of resistance, guiding personalized approaches in treatment-resistant cancer. Novita is on track to begin enrollment in its pivotal Phase 3 study of NP-G2-044 + PLD in platinum resistant ovarian cancer in the third quarter of 2025. About Novita's Pioneering Research in Fascin Inhibition Cancer metastasis is the primary cause of over 90% of cancer-related deaths, yet there is currently no drug on the market specifically targeting metastasis. Furthermore, while Immuno-Oncology (IO) therapies, particularly immune checkpoint inhibitors, have made significant strides in cancer treatment, a large proportion of patients do not respond to existing IO treatments. Novita aims to address both of these critical medical needs by developing fascin inhibitors, which target a key protein involved in tumor cell motility and highly expressed in tumor cells and antigen-presenting cells within tumor tissues. The Company's lead asset, NP-G2-044, is a small-molecule fascin inhibitor that has demonstrated the ability to block metastasis in both preclinical and clinical studies. Additionally, when combined with immune checkpoint inhibitors, NP-G2-044 has shown potential to reinvigorate anti-tumor immune responses. Novita's multicenter Phase 2 clinical trial, titled "NP-G2-044 as Monotherapy and Combination Therapy in Patients with Advanced or Metastatic Solid Tumor Malignancies," is currently ongoing. About Novita Pharmaceuticals, Inc. Novita Pharmaceuticals, Inc. is a privately held, clinical-stage biopharmaceutical company focused on developing groundbreaking therapies using its proprietary fascin inhibitor technology to prevent and treat cancer metastasis while simultaneously enhancing anti-cancer immune responses. For more information, visit Cautionary Note Regarding Forward-Looking Statements This press release contains certain forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in the forward-looking statements. These statements are based on a number of assumptions and estimates that are inherently subject to significant uncertainties and contingencies, many of which are beyond the Company's control, and respect future business decisions, which are subject to change. Among those factors that could cause actual results to differ materially from those described in the forward-looking statements are the risks associated with the Company's being a development stage company with uncertain revenue streams; uncertain results or outcomes during clinical trials; failure to raise necessary capital in the future; the loss of key personnel; competition from other larger, better-capitalized peers; the Company's reliance on incorrect assumptions regarding the market for its products, the costs of developing, manufacturing and marketing the Company's products, and the timing and receipt of regulatory approval for the Company's products; adverse economic conditions; and other risks. In light of the significant uncertainties inherent in the forward-looking statements, the inclusion of any such statement should not be regarded as a representation by Novita or any other person that the Company's objectives or plans will be achieved. Media Contact: Argot Partners (media) David Rosen 212.600.1902 [email protected] Investor Contact: Argot Partners (investors) Noor Pahlavi 212.600.1902 [email protected] SOURCE Novita Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

近期，安进公司（Amgen）的PRMT5抑制剂AMG 193在临床试验中表现不佳，引发了业界对其未来前景的担忧。本文将结合ESMO 2024年会上公布的最新数据和相关报道，对AMG 193的临床表现、安全性以及未来发展方向进行分析。一、AMG 193的临床表现 AMG 193是一种MTA合作型PRMT5抑制剂，旨在通过合成致死机制特异性地杀死MTAP缺失的肿瘤细胞。在2024年ESMO年会上，安进公布了AMG 193的最新临床试验数据。结果显示，在800mg和1200mg每日一次以及600mg每日两次的剂量下，AMG 193的确认客观缓解率（ORR）仅为11%（7/65）。具体到不同肿瘤类型，非小细胞肺癌（NSCLC）的ORR为12%（2/17），胰腺导管腺癌（PDAC）的ORR为9%（2/23），胆道癌（BTC）的ORR为11%（2/19），食管/胃癌（E/G）的ORR为17%（1/6）。这一结果相较于去年Triple Meeting上公布的28%的ORR有明显下降，令人失望。二、安全性问题 在安全性方面，AMG 193的表现也不尽如人意。在1200mg每日一次的剂量下，有18%的患者出现了3级治疗相关不良事件（TRAEs），包括呕吐和低钾血症等。此外，不同剂量下共报告了8例剂量限制性毒性（DLTs），其中2例发生在1200mg每日一次的剂量组。这些安全性问题对AMG 193的临床应用前景构成了挑战。三、联合试验的终止 AMG 193与Ideaya Biosciences的MAT2A抑制剂IDE397的联合临床试验近期被终止。这一决定是基于双方对临床数据的评估，认为联合用药并未带来预期的疗效提升。Ideaya对IDE397本身仍充满信心，并计划与其他PRMT5抑制剂进行联合试验。这一消息对AMG 193的未来开发无疑是雪上加霜。四、竞争对手的表现 在PRMT5抑制剂领域，安进面临着来自其他公司的激烈竞争。Bristol Myers Squibb通过收购Mirati获得了MRTX1719，该药物在临床试验中表现出更高的ORR，达到了33%。此外，Tango Therapeutics和AstraZeneca也在积极推进各自的PRMT5抑制剂项目，分别计划在今年和去年报告临床数据。这些竞争对手的强劲表现进一步凸显了AMG 193的劣势。五、国内PRMT5抑制剂的发展 近年来，国内药企在PRMT5抑制剂领域也取得了显著进展。例如，南京圣和药业的SH3765是国内首个获批的PRMT5抑制剂，具有自主知识产权。先声药业的SIM0272显示出高抑制活性和高选择性，有助于降低血液毒性。勤浩医药的GH56和湃隆生物的GTA182等新一代PRMT5抑制剂也展现出了良好的前景。这些国内药物的研发进展为患者带来了更多希望，同时也加剧了全球PRMT5抑制剂市场的竞争。六、未来展望 尽管AMG 193在临床试验中表现不佳，但安进并未放弃对其的开发。公司计划继续推进AMG 193的单药和联合治疗试验，以探索更优的剂量方案和治疗策略。此外，安进也在积极布局其他PRMT5抑制剂项目，如AM-9747，以应对AMG 193可能的失败。未来，PRMT5抑制剂的研发将更加注重特异性和安全性，以提高治疗效果并降低不良反应。 综上所述，AMG 193在临床试验中面临诸多挑战，其未来前景不容乐观。然而，随着对PRMT5抑制机制的深入研究和新药物的不断涌现，相信在不久的将来，患者将迎来更多有效的治疗选择。 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。