Neratinib maleate

2025年1月26日，复宏汉霖（2696.HK）宣布，公司两项创新药抗PD-1单抗H药 汉斯状®和创新型抗HER2单抗HLX22的最新研究结果在2025年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）上以壁报形式发布。 H药 汉斯状®为复宏汉霖自主研发的重组人源化抗PD-1单抗注射液，也是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国和多个东南亚国家获批上市。以临床需求为导向，公司围绕H药进行了差异化、多维度的适应症布局，广泛覆盖肺癌、消化道肿瘤等高发大癌种。截至目前，H药已在中国获批用于治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）、食管鳞状细胞癌（ESCC）和非鳞状非小细胞肺癌（nsNSCLC），惠及患者超过90,000人。此外，公司亦积极推进H药在更多差异化适应症中的创新联合疗法，探索在结直肠癌、胃癌和局限期小细胞肺癌（LS-SCLC）等领域的应用，为更多患者带去治疗希望。 HLX22为复宏汉霖自AbClon, Inc.许可引进、并后续自主研发的靶向HER2的创新型单克隆抗体。临床前研究表明，HLX22与曲妥珠单抗联合治疗能够协同抑制肿瘤细胞增殖和诱导细胞凋亡，在体内和体外均表现出增强的抗肿瘤活性。HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性胃/胃食管交界部（G/GEJ）癌的II期临床研究结果显示，在曲妥珠单抗联用化疗的基础上加入HLX22可明显改善HER2阳性G/GEJ癌患者一线治疗的效果，且安全性可控[1,2]。目前，HLX22联合曲妥珠单抗和化疗一线治疗HER2阳性晚期G/GEJ的国际多中心III期临床试验相继获中国、美国、日本、澳大利亚临床试验许可，并于中国完成首例患者给药。 本次ASCO GI大会上发布的研究数据详情如下： H药 汉斯状® 论文题目 斯鲁利单抗联合贝伐珠单抗和XELOX对比安慰剂联合贝伐珠单抗和XELOX一线治疗转移性结直肠癌的疗效和亚组分析更新：一项II/III期研究 试验设计 共有114名未接受过系统治疗的mCRC患者以1：1的比例随机分配至斯鲁利单抗治疗组（n = 57）或安慰剂治疗组（n = 57）。两组患者分别接受斯鲁利单抗（300 mg）联合贝伐珠单抗（7.5 mg/kg）和XELOX（A组）或安慰剂联合贝伐珠单抗和XELOX（B组），每3周一次。分层因素包括PD-L1表达水平、ECOG PS评分和原发肿瘤部位。主要终点是由独立影像学评审委员会（IRRC）根据RECIST 1.1评估的无进展生存期（PFS）。次要终点包括其他有效性终点、安全性、药代动力学、生物标志物探索和生活质量评估。 结果 2期研究部分，截至数据截止日期2024年6月30日，在改良的意向治疗人群（n = 112；A组中有两例患者未接受任何研究治疗）中，与B组相比，在A组中观察到PFS（16.6m vs. 10.7m，HR 0.66，95%Cl 0.37–1.19）和DOR（17.7m vs. 11.3m，HR 0.45，95% Cl 0.20–0.98）的持续改善。在微卫星稳定型（MSS）患者中也观察到了类似的PFS和OS获益趋势（PFS：16.8m vs. 10.1m，HR 0.65，95% Cl 0.33–1.29；OS：23.5m vs. 20.2m，HR 0.79，95% Cl 0.45–1.38）。大多数irAEs为轻度（1-2级）；A组中12.7%的患者发生了≥3级的irAEs；B组中有1.8%的患者发生了≥3级的irAEs。 结论 中位随访时间为31.0个月时，在贝伐珠单抗和XELOX基础上加入斯鲁利单抗一线治疗mCRC患者（包括MSS患者）展现了生存获益，并维持了可控的安全性特征。该方案有望成为mCRC一线治疗方案。本研究在MSS mCRC患者中开展的3期部分目前正在进行中(NCT04547166)，以进一步评估斯鲁利单抗联合贝伐珠单抗和XELOX作为MSS mCRC的一线治疗方案。 论文题目 PD-1抑制剂联合化疗对比化疗转化治疗局晚期伴腹主动脉旁淋巴结转移胃癌行D2根治术的疗效和安全性：一项单中心、回顾性研究 试验设计 本研究回顾性收集了133例浙江省肿瘤医院2011年1月至2024年2月的伴第16a2/b1腹主动脉旁淋巴结转移胃癌的患者信息，其中接受化疗联合免疫治疗的患者为队列A (n=62)，仅接受化疗治疗的患者为队列B(n=71)。主要研究终点为病理完全缓解率 (pCR) ，次要研究终点为安全性、主要病理学缓解率 (MPR)、R0切除率和总生存期。 结果 所有入组的133例患者中，95例(71.4%) 患者为男性，中位年龄为66岁。接受化疗联合免疫治疗的队列A中，有32例患者使用斯鲁利单抗，30例患者使用替雷利珠单抗。队列A和队列B的主要研究终点pCR率分别为37.1% vs 4.2%（p＜0.001），次要研究终点MPR率为58.1% vs. 22.5%（p＜0.001），R0切除率为100% vs. 98.6%（p=0.348），2年OS率为90.3% vs. 62.9%（p=0.011）。亚组数据提示：PD-L1 CPS≥5的患者pCR和MPR获益最高。治疗期间，有122例 (91.7%)患者经历了任意级别的不良事件，所有不良事件均可控，无治疗相关死亡事件发生。 结论 相比于化疗，增加PD-1抑制剂可显著提升伴腹主动脉旁淋巴结转移胃癌的病理完全缓解率和预后，并未增加不良事件的发生。 HLX22 论文题目 HLX22联合曲妥珠单抗和XELOX用于HER2阳性局部晚期或转移性胃癌/胃食管连接部癌（G/GEJC）的一线治疗：包含更多患者的更新结果 试验设计 本研究入组局部晚期或转移性HER2阳性G/GEJC且未接受过全身抗肿瘤治疗的患者。研究由两部分组成，本文报告第2阶段的结果。符合条件的患者按1：1比例随机分组，接受HLX22 15 mg/kg + 曲妥珠单抗 + XELOX或安慰剂 + 曲妥珠单抗+ XELOX治疗，每3周为一个周期。主要终点为独立影像评估委员会（IRRC）评估的无进展生存期（PFS）和根据实体瘤疗效评价标准（RECIST）v1.1的客观缓解率（ORR）。次要终点包括其他有效性终点和安全性终点。 结果 截至2024年6月30日，共有62例患者（31 vs 31）被随机分配到相应治疗组，其中51例患者（82.3%）为男性。中位随访时间分别为20.3m和24.0m。有效性结果见表1。治疗期不良事件（TEAEs）分别发生于30例（96.8%）和31例（100%）患者。与HLX22或安慰剂相关的≥3级TEAE分别发生于9例（29.0%）和6例（19.4%）患者。在安慰剂 + 曲妥珠单抗 + XELOX组中，有1例患者（3.2%）发生了HLX22/安慰剂相关的5级TEAE。 结论 在曲妥珠单抗联合XELOX基础上加入HLX22一线治疗HER2阳性G/GEJC展现了生存获益，且安全性可控。 【参考文献】 [1] Li N, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2. [2] Jin Li, et al., HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study. JCO 42, 354-354(2024). 关于复宏汉霖 复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已有6款产品在中国获批上市，3款产品在国际获批上市，4个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。 复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖50多个分子，并全面推进基于自有抗PD-1单抗H药 汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗）以及汉奈佳®（奈拉替尼）。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。 Results from Clinical Trials of Two Henlius’ Innovative Products Released at ASCO GI 2025 Shanghai, China, January 26, 2025 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that the latest clinical data of two Henlius novel products, the anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab) and an innovative anti-HER2 mAb HLX22, were presented in poster sessions at the 2025 ASCO Gastrointestinal Cancers Symposium (ASCO GI). HANSIZHUANG (serplulimab) is a recombinant humanised anti-PD-1 monoclonal antibody（mAb）injection independently developed by Henlius, and the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC. Up to date, it has been approved in China and several Southeast Asian countries. Underpinned by the patient-centric strategy, Henlius has carried out a differentiated and multi-dimensional layout in the field of gastrointestinal cancer and lung cancer, covering a wide variety of indications. In China, it has been approved by the NMPA for the treatment including squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC), benefiting over 90,000 patients. Moreover, a wide variety of clinical trials on immuno-oncology combination therapies in differentiated indications has been initiated by the company to further explore the efficacy of HANSIZHUANG for the treatment of patients with metastatic colorectal cancer (mCRC), gastric cancer (GC), and limited-stage small cell lung cancer (LS-SCLC),etc. HLX22 is an innovative anti-HER2 mAb introduced from AbClon, Inc. and further investigated and developed by Henlius. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab synergistically inhibited tumour cell proliferation and apoptosis, which led to enhanced anti-tumour activity in vitro and in vivo. HLX22-GC-201, the phase 2 clinical trial of HLX22 combined with trastuzumab showed that adding HLX22 to HLX02 (trastuzumab for injection) + XELOX improved survival and anti-tumour response in patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer in the first-line setting, with a manageable safety profile[1,2]. Up to date, the phase 3 international multicenter clinical study of HLX22 in combination of trastuzumab and chemotherapy for the treatment of HER2 positive advanced G/GEJ cancer has received regulatory approvals in China, the U.S., Japan and Australia, respectively. And the first subject has been dosed for this MRCT in China. The latest data of the studies released at ASCO GI 2025 are as follows: HLX10 Title Updated efficacy and subgroup analysis of first-line serplulimab plus bevacizumab and XELOX versus placebo plus bevacizumab and XELOX in metastatic colorectal cancer: a phase 2/3 study Study design A total of 114 patients with mCRC and no prior systemic therapy were randomized 1:1 (serplulimab arm, n = 57; placebo arm, n = 57) to receive intravenous (IV) serplulimab (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (group A) or placebo plus bevacizumab and XELOX (group B) once every 3 weeks. Stratification factors were PD-L1 expression level, ECOG PS score, and primary tumor site. The primary endpoint was independent radiological review committee (IRRC)-assessed PFS per RECIST 1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments. Results In the phase 2 part, by the data cutoff of June 30, 2024, sustained improvements in PFS (16.6 vs. 10.7 months, stratified HR 0.66, 95% CI 0.37–1.19) and DOR (17.7 vs. 11.3 months, stratified HR 0.45, 95% CI 0.20–0.98) were observed for patients in group A compared to group B in the modified intent-to-treat population (n = 112; two patients in group A did not receive any intended study treatment). A trend of PFS and OS benefits was similarly observed for the patients with a microsatellite stable (MSS) status (PFS: 16.8 vs. 10.1 months, stratified HR 0.65, 95% CI 0.33–1.29; OS: 23.5 vs. 20.2 months, stratified HR 0.79, 95% CI 0.45–1.38). Most irAEs were mild (grade 1–2); grade ≥3 irAEs occurred in 12.7% of the patients in group A, and 1.8% of the patients in group B. Conclusion With a median follow-up duration of 31.0 months, improved survival benefits demonstrated with the addition of serplulimab were maintained in the first-line treatment of mCRC patients including those with MSS status alongside a manageable safety profile. Serplulimab plus bevacizumab and XELOX has promising potential to be an alternative first-line option in mCRC. The phase 3 part of this study conducted in patients with MSS mCRC is currently ongoing (NCT04547166). Title Safety and Efficacy of Perioperative Chemotherapy Combined with PD-1 Inhibitor versus Chemotherapy with D2 plus Gastrectomy and PAND in Gastric Cancer with PAN Metastasis: A Single-Center Retrospective Cohort Study Study design We retrospectively reviewed medical records of gastric cancer patients with isolated No. 16a2/b1 PAN metastasis treated at Zhejiang Cancer Hospital, Hangzhou, China, between January 2011 and February 2024. The analysis included 133 patients; those who received immunochemotherapy were assigned to Group A (n=62), and those who received chemotherapy alone were assigned to Group B (n=71). The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included safety, major pathological response (MPR), R0 resection, and survival. Results In the entire cohort, 95 patients (71.4%) were male, with a median age of 66 years. All patients in Group A received anti-PD-1 monoclonal antibodies as immunotherapy, with 32 patients treated with serplulimab and 30 patients treated with tislelizumab. A total of 26 patients (19.5%) achieved pCR. The pCR and MPR rates were significantly higher in Group A (Table 2). The 2-year OS rates for Group A and Group B were 90.3% and 62.9% (P=0.011). Subgroup analysis of Group A showed patients with PD-L1 CPS ≥5 have a better pCR and MPR CPS <5. A total of 122 patients (91.7%) experienced any grade of adverse events (AEs) during perioperative treatment, 56 (90.3%) in Group A and 66 (92.9%) in Group B. All AEs were well-controlled, and no treatment-related deaths were reported. Conclusion The addition of a PD-1 inhibitor to chemotherapy significantly improves the pathological response rate and prognosis in gastric cancer patients with PAN. Notably, the combination did not increase adverse events. HLX22 Title HLX22 plus trastuzumab and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC): Updated results with additional patients Study design Patients with locally advanced or metastatic HER2-positive G/GEJC and no prior systemic antitumor therapy were enrolled. Herein reported are results from Stage 2 of the study. Eligible patients were randomized to receive either HLX22 + trastuzumab + XELOX or placebo + trastuzumab + XELOX in 3-week cycles. Primary endpoints were independent radiology review committee (IRRC)-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included other efficacy and safety endpoints. Results As of June 30, 2024, 62 patients were randomized to the respective groups (31 vs 31), of whom 51 (82.3%) patients were male. Median follow-up duration was 20.3 and 24.0 months for the respective groups. The efficacy results are shown in Table 1. Treatment-emergent adverse events (TEAEs) were reported in 30 (96.8%) and 31 (100%) patients, and HLX22- or placebo-related TEAEs of grade 3 or higher were reported in 9 (29.0%) and 6 (19.4%) patients in the respective groups. One patient (3.2%) in the placebo + trastuzumab + XELOX group had a grade 5 HLX22-/placebo-related TEAE.  Conclusion With a manageable safety profile, the addition of HLX22 to first-line treatment with trastuzumab plus XELOX conferred survival benefit for HER2-positive G/GEJC patients. About Henlius Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, and 4 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab), HANSIZHUANG, the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 联系方式 媒体：PR@Henlius.com 投资者：IR@Henlius.com