Cancer Immunology, Immunotherapy发表H药 汉斯状®联合汉贝泰®治疗肝细胞癌II期临床研究最新数据

NCT03973112研究是一项开放、多中心、单臂临床II期研究，旨在评估斯鲁利单抗单药或联合HLX04在晚期肝细胞癌患者中的安全性和疗效。本研究数据于2022年首次发表于肝病学知名期刊Liver Cancer，公布了该联合疗法在既往经受过治疗患者中的数据。患者每2周静脉输注一次斯鲁利单抗3 mg/kg联合不同剂量的HLX04 5 mg/kg或10 mg/kg。研究结果显示，H药联合汉贝泰^®在先前经受治疗的晚期肝细胞癌患者中具有良好的安全性，并展现出明显的抗肿瘤活性。

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。

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，惠及患者逾9万人。针对消化道肿瘤，复宏汉霖积极推进H药与公司其他产品的协同以及与创新疗法的联合，广泛布局结直肠癌、胃癌、肝癌和食管癌等高发大瘤种。H药联合化疗治疗不可切除局部晚期/复发或转移性食管鳞癌（ESCC）的一线治疗方案已于2023年9月获得中国国家药监局（NMPA）批准上市，为我国食管鳞癌患者带来了免疫治疗新选择。与此同时，H药联合化疗用于新辅助/辅助治疗胃癌已进入III期临床研究，有望使胃癌患者在前线便从肿瘤免疫疗法中获益。此外，H药联合贝伐珠单抗联合化疗用于一线治疗转移性结直肠癌（mCRC）患者的国际多中心临床研究（ASTRUM-015）已于2024年启动III期临床阶段研究并于中国、印度尼西亚和日本完成首例受试者给药，H药有望成为全球首个一线治疗mCRC的抗PD-1单抗，填补一线免疫治疗mCRC的临床空白。

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。

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.  

媒体：PR@Henlius.com

投资者：IR@Henlius.com