Cancer Immunology, Immunotherapy发表H药汉斯状®联合汉贝泰®治疗肝细胞癌II期临床研究

复星医药

2025/01/24

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PD-1 肝细胞癌贝伐珠单抗斯鲁利单抗阿替利珠单抗

近日，复星医药子公司复宏汉霖H药汉斯状^®（斯鲁利单抗）联合汉贝泰^®（贝伐珠单抗，HLX04）在晚期肝细胞癌（HCC）患者中开展的II期临床研究（NCT03973112）最新数据发表于Cancer Immunology, Immunotherapy（IF 4.6）。研究结果显示，H药联合汉贝泰^®在先前未经治疗的晚期肝细胞癌患者中具有可控的安全性，并展现出明显的抗肿瘤活性。

Liver Cancer

此次在Cancer Immunology, Immunotherapy发表的最新数据聚焦既往未接受系统抗肿瘤治疗的患者（n=61）的数据，患者每2周静脉输注一次斯鲁利单抗3 mg/kg联合HLX04 10 mg/kg。主要终点为安全性，次要终点包括客观缓解率（ORR）、总生存期（OS）、无进展生存期（PFS）、持续缓解时间（DoR）等。截至2023年2月7日，斯鲁利单抗联合HLX04展现出良好的安全性和耐受性。在可评估有效性分析集（EES）人群中（n=58），经独立影像评估委员会评估的ORR为29.3%（95%置信区间[CI]：18.1–42.7），中位PFS为7.3个月（95% CI：2.8–11.0），中位DoR为12.7 个月 (95% CI: 4.5–不可评估)。在17名有缓解的患者中，12名（70.6%）DoR达到或超过6个月。该研究结果显示，斯鲁利单抗、HLX04及其联合疗法在既往未经治疗的晚期HCC患者中的安全性特征，与既往报道的抗PD-1单抗单药、贝伐珠单抗单药以及阿替利珠单抗联合贝伐珠单抗的治疗方案均一致。此外，相较于现有同类抗PD-(L)1产品，斯鲁利单抗和HLX04联合疗法在中国人群中展现出相似或更大生存获益。该研究数据有望为斯鲁利单抗联合抗血管生成药物在HCC一线的临床实践提供依据。

未来，复宏汉霖将持续加码创新，以临床需求为先导，继续高效地为全球患者提供更多可负担、疗效更好的治疗方案。

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。

Serplulimab plus HLX04 for HCC: Phase 2 Results Published in Cancer Immunology, Immunotherapy

Recently, the latest data from Henlius' Phase II clinical study (NCT03973112) of serplulimab (HANSIZHUANG) in combination with HLX04 (bevacizumab) for the treatment of advanced hepatocellular carcinoma (HCC) were published in Cancer Immunology, Immunotherapy. The study demonstrated that the combination therapy of serplulimab with HLX04 showed a manageable safety profile and promising anti-tumor efficacy in previously untreated patients with advanced HCC.

The NCT03973112 study is an open-label, multicenter, single-arm, phase 2 clinical trial aimed to evaluate the safety and efficacy of serplulimab as monotherapy or in combination with HLX04 in patients with advanced hepatocellular carcinoma (HCC). Data from this study were first published in the renowned hepatology journal Liver Cancer in 2022, presenting the results of the combination therapy in patients who had received prior systemic therapy. Patients received intravenous infusions of serplulimab at 3 mg/kg every two weeks in combination with different doses of HLX04 (5 mg/kg or 10 mg/kg). The study results demonstrated that the combination of serplulimab and HANBEITAI showed a manageable safety profile and favorable anti-tumor activity in patients with previously treated advanced HCC.

The latest data published in Cancer Immunology, Immunotherapy focus on the subgroup of patients (n=61) who had not previously received systemic treatment. These patients received intravenous infusions of serplulimab (3 mg/kg) combined with HLX04 (10 mg/kg) every two weeks. The primary endpoint was safety, while secondary endpoints included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DoR), among others. As of February 7, 2023, the combination therapy of serplulimab and HLX04 was well tolerated in patients with aHCC in the first-line setting. In the efficacy evaluable set (EES) of patients (n=58), the ORR was 29.3% (95% CI: 18.1–42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. The median PFS was 7.3 months (95% CI: 2.8–11.0), and the median DoR was 12.7 months (95% CI: 4.5–not evaluable [NE]). Notably, among the 17 patients who achieved a response, 12 (70.6%) had a DoR of at least 6 months.

The study results showed that the safety profile of serplulimab, HLX04, and their combination therapy in patients with previously untreated advanced HCC was consistent with those reported for monotherapy with anti-PD-1 inhibitors, bevacizumab, and the combination of atezolizumab plus bevacizumab. Moreover, compared to other PD-(L)1 inhibitors, the combination therapy of serplulimab and HLX04 conferred similar or greater survival benefit in the Chinese population. These findings may provide a basis for the clinical application of serplulimab in combination with anti-angiogenic agents as a first-line treatment for HCC.

HANSIZHUANG, the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC developed by Henlius, has been approved in China and several Southeast Asian countries, benefiting over 90,000 patients to date. Focusing on gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. This includes extensive clinical development in high-incidence cancers such as colorectal cancer, gastric cancer, liver cancer, and esophageal cancer. In September 2023, the combination of HANSIZHUANG and chemotherapy for the first-line treatment of unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC) was approved by the National Medical Products Administration (NMPA), offering a new immunotherapy option for patients with ESCC. Additionally, HANSIZHUANG has led the way with a phase 3 clinical study on neoadjuvant/adjuvant therapies for gastric cancer, striving to benefit gastric cancer patients from the early line of immunotherapy. Furthermore, the international multicenter clinical study (ASTRUM-015) of HANSIZHUANG in combination with bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer (mCRC) has launched its phase 3 stage and completed the first patient dosing in China, Japan, and Indonesia. With the accelerated progress, HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for previously untreated mCRC and fill the clinical gap in first-line immunotherapy in these patients.

Looking forward, Henlius will actively improve efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.

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.