2024年8月8日，复宏汉霖（2696.HK）书记，公司自主开导的改进型抗TIGIT Fc交融卵白HLX53聚会H药 汉斯状（斯鲁利单抗，HLX10）及汉贝泰（贝伐珠单抗【ATI-014】REAL WORLD 2 ゆりあ2004-08-26アタッカーズ&$in mad90分钟，HLX04）在局部晚期或鼎新性肝细胞癌患者中开展的II期临床熟识（NCT06349980）完成首例患者给药。

肝癌是大师范围内常见的恶性肿瘤。据GLOBOCAN统计，2022年大师肝癌发病数和死亡数差异为87万及76万例 [1]。在中国，原发性肝癌是第五大最常见的癌症，以登科二约莫死癌症。2022年中国新发肝癌病例约37万例，肝癌死亡病例32万例。其中，肝细胞癌是最常见的原发性肝癌类型，约占总病例数的75-85% [2]。因原发性肝癌起病隐退，早期无症状或症状不彰着，阐发飞速，确诊时大大批患者如故达到局部晚期或发生远方鼎新，颐养艰难，预后很差，五年生涯率仅约18% [3]。对晚期肝癌患者来说，当今一线颐养以靶向颐养和免疫颐养为主，免疫扼制剂及抗血管生成药物的聚会颐养表露出权贵的临床抗肿瘤活性和生涯获益 [2]，但仍有较大比例的患者并不成从中获益，导致肿瘤复发或阐发，尚存在要紧的临床需求以扩大免疫颐养的受益东说念主群，并进步免疫颐养的疗效。

含免疫球卵白和ITIM结构域的T细胞免疫受体（T cell immunoglobulin and ITIM domain， TIGIT）是连年来肿瘤免疫颐养中最有远景和后劲的靶点之一。TIGIT是一种扼制性受体，在淋巴细胞中抒发，包括当然杀伤（NK）细胞、活化的CD8+ T和CD4+ T细胞以及Treg（调度性T细胞）等 ，其要紧配体为主要抒发于APC（抗原提呈细胞）或肿瘤细胞名义的CD155（脊髓灰质炎病毒受体，PVR）[4]。手脚免疫搜检点卵白，TIGIT可通过多种作用机制扼制固有和恰当性免疫，在肿瘤免疫扼制中的“踩刹车”作用和PD-1/PD-L1访佛。多项盘问数据表露，TIGIT扼制剂有望颐养多种晚期癌症，包括肺癌、胃癌、玄色素瘤和多发性骨髓瘤等多种实体瘤和淋巴瘤。且已有临床前盘问标明，TIGIT靶点可能与 PD-1 通路产生协同效应，同期阻断TIGIT和PD-1/PD-L1信号通路优于单独阻断任一通路，可增强抗肿瘤活性[5]。

HLX53是复宏汉霖自主研发的改进型抗TIGIT的Fc交融卵白，由重链抗体的可变区（VHH）和野生型 IgG1的Fc端构成。临床前盘问收尾标明，HLX53具有优异的肿瘤扼制效力且安全性致密。公司亦于2022年入手了一项I期临床盘问，以评估HLX53在晚期/鼎新性实体瘤患者中的安全性、耐受性、药代能源学特征及初步疗效。鉴于抗PD-1/PD -L1单抗等免疫扼制剂及抗血管生成药物在晚期肝细胞癌患者中取得的致密疗效，及TIGIT与PD-1/PD-L1信号通路的协同效应，复宏汉霖旨在通过开展此项盘问，进一步探索抗PD-1单抗与TIGIT扼制剂的双免疫颐养与抗血管靶向疗法的组合，以期为晚期肝细胞癌患者带来更高的临床获益。

复宏汉霖从临床需求启航，当今在PD-1/L1、CTLA-4、LAG-3等免疫搜检点全面布局，为免疫聚会颐养的探索创造更多可能。同期，公司充分讹诈自有管线掩盖肿瘤特异性靶点、抗血管生成靶点和肿瘤免疫靶点等多个类别的性情，助力H药与自有单抗产物、化疗等颐养妙技开展聚会颐养，有助于充分挖掘免疫疗法的颐养后劲，为大师患者带去高品性、可包袱的改进颐养决策。

【参考文件】

[1] Globocan 2022 (version 1.1) - 08.02.2024；.fr/today/en/dataviz/bars-compare-populations?mode=cancer&group_populations=1&cancers=11&populations=900&sort_by=value1&types=0_1&key=total

[2]原发性肝癌诊疗指南（2024年版）

色表姐

[3] Asafo-Agyei KO， Samant H. Hepatocellular Carcinoma. 2023 Jun 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32644603.

[4] Chauvin， Joe-Marc， and Hassane M Zarour. “TIGIT in cancer immunotherapy.”Journal for immunotherapy of cancervol. 8，2 (2020): e000957. doi:10.1136/jitc-2020-000957.

[5] Chu， Xianjing et al. “Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials.” Molecular cancer vol. 22，1 93. 8 Jun. 2023， doi:10.1186/s120-3.

对于NCT06349980

本盘问为一项立时、双盲、多中心的II期临床盘问，旨在评估HLX53聚会汉斯状及汉贝泰对比安危剂聚会汉斯状及汉贝泰在未经颐养的局部晚期或鼎新性肝细胞癌患者中的灵验性、安全性和耐受性。盘问分为两个部分：A部分为安全导入期，将取舍“3+3”剂量递加盘算，及格的受试者将领受每三周一次静脉输注不同剂量HLX53（1000 mg或2000 mg）聚会汉斯状（300 mg）及汉贝泰（15 mg/kg）的颐养；B部分为初步疗效探索期，及格的受试者将按照1:1:1的比例，立时辰派领受每三周一次静脉输注HLX53（1000 mg）、HLX53（2000 mg）或安危剂差异聚会汉斯状（300 mg）及汉贝泰（15 mg/kg）的颐养。A部分的主要止境为安全性和耐受性，评估每个剂量组中发生剂量规矩毒性（DLT）事件的患者比例。B部分的主要止境为由寥寂影像评估委员会证据RECIST v1.1评估的客不雅缓解率和无阐发生涯期。

对于复宏汉霖

复宏汉霖（2696.HK）是一家国外化的改进生物制药公司，致力于于于为大师患者提供可包袱的高品性生物药，产物掩盖肿瘤、本身免疫疾病、眼科疾病等规模，已在中国上市5款产物，在国外获批上市3款产物，23项恰当症获批，3个上市请求差异获中国药监局和欧盟EMA受理。自2010年树立以来，复宏汉霖已建成一体化生物制药平台，高效及改进的自主中枢才调结合研发、分娩及买卖运营全产业链。公司已诞生完善高效的大师改进中心，按照国外药品分娩质地科罚法式（GMP）圭臬进行分娩和质地管控，不休夯实一体化笼统分娩平台，其中，公司买卖化分娩基地已接踵得到中国、欧盟和好意思国GMP认证。

复宏汉霖前瞻性布局了一个多元化、高质地的产物管线，涵盖50多个分子，并全面推动基于自有抗PD-1单抗H药汉斯状的肿瘤免疫聚会疗法。继国内首个生物访佛药汉利康（利妥昔单抗）、自主研发的中好意思欧三地获批单抗生物访佛药汉曲优（曲妥珠单抗，好意思国商品名：HERCESSI，欧洲商品名：Zercepac）、汉达远（阿达木单抗）和汉贝泰（贝伐珠单抗）接踵获批上市，改进产物汉斯状（斯鲁利单抗）已获批用于颐养微卫星高度不镇定（MSI-H）实体瘤、鳞状非小细胞肺癌、芜俚期小细胞肺癌和食管鳞状细胞癌，并成为大师首个获批一线颐养小细胞肺癌的抗PD-1单抗。公司亦同步就16个产物在大师范围内开展30多项临床熟识，对外授权全面掩盖西洋主流生物药阛阓和宽阔新兴阛阓。

First Patient Dosed of Phase 2 Clinical Trial of Novel Anti-TIGIT Fc Fusion Protein in Combination with Serplulimab Plus HANBEITAI for the First-line Treatment of Locally Advanced or Metastatic Hepatocellular Carcinoma Patients

Shanghai， China， August 8， 2024 - Shanghai Henlius Biotech， Inc. (2696.HK) announced that the first patient has been dosed in a phase 2 clinical trial (NCT06349980) of HLX53， an anti-TIGIT Fc fusion protein， in combination with HANSIZHUANG (serplulimab， HLX10) and HANBEITAI (bevacizumab， HLX04) for the first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC).

Liver cancer is one of the most prevalent malignancy in the world. According to GLOBALCAN 2022， there are about 870，000 new cases diagnosed and 760，000 deaths for the tumour in the globe[1]. Meanwhile，primaryliver cancer (PLC)is the fifth most common cause and the second mortality cancer in China， with about 370，000 new cases and 320，000 deaths in 2022. From which， hepatocellular carcinoma (HCC) is the predominant pathological type ofPLC， which accounts for between 75% and 85% of liver cancer cases[2]. Due to its insidious onset， lack of symptom in its early stage， and quick progression， PLC usually has been in its locally advanced stage or develops distant metastasis when it is diagnosed. As a result， the management becomes extremely difficult and the prognosis usually is poor. The 5-year survival rate of PLC is only about 18%[3]. For patients with advanced liver cancer， the first-line treatment is based on targeted therapy and immunotherapy. And the standard therapy (combination therapiesof immune inhibitor plus anti-angiogenic treatment)have shown significant clinical anti-tumour efficacy and survival benefit[2]. However， some patients failed to benefit from the standard therapy and suffered from recurrence or progression of the disease. Thers is still an urgent clinical need to further expand the benefit population with advanced liver cancer and improve the efficacy of immunotherapy.

T-cell immunoglobulin and ITIM domains (TIGIT) has emerged as popular inhibitory checkpoint receptor， which is mainly expressed on natural killer (NK) cells， activated CD8+ T and CD4+ T cells， and T regulatory cells. TIGIT binds to the ligand CD155 (poliovirus receptor， PVR)[4]， mainly expressed on antigen-presenting cells (APC) or the surface of tumour cells， to down-regulate T cell and NK cell functions. As an immune checkpoint protein， TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as “brakes” like PD-1/PD-L1 does to stop T cells from attacking tumours. Studies have shown that TIGIT inhibitor are effective against lung cancer， gastric cancer， melanoma， multiple myeloma， etc. Moreover， TIGIT has shown a synergistic effect with the PD-1 pathway in preclinical studies， indicating that simultaneous blocking of TIGIT and PD-1/PD-L1 signaling pathways is superior to blocking either pathway alone， which can enhance anti-tumour activity[5].

HLX53 is an anti-TIGIT Fc fusion protein independently developed by Henlius， consisting of variable domain of heavy chain of heavy-chain antibody (VHH) and wildtype IgG1 Fc. Pre-clinical studies have demonstrated that HLX53 exhibits excellent tumour inhibition with good safety. In addition， Henlius has initiated a phase 1 study to evaluate the safety， tolerability， pharmacokinetics characteristics and preliminary efficacy of HLX53 in patients with advanced/metastatic solid tumors.Consideringthe good efficacy ofimmune checkpoint inhibitor such asanti-PD-1/PD-L1 antibody plusanti-angiogenic drugin the first-line treatment of patients with advanced HCC， as wellasthe synergistic effect of TIGIT and PD-1/PD-L1 signaling pathway，Henlius intends to furthercombine TIGIT inhibitor based on the standard therapy in order to bring greater clinical benefits to patients with advanced HCC.

Underpinned by the patient-centric strategy， Henlius has achieved an overall layout of the immune checkpoint products of PD-1/L1， CTLA-4， LAG-3， etc.， proactively exploring immuno-oncology combination therapy. Meanwhile， Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target， angiogenesis target， immunotherapeutic target， etc. and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications， committing to bringing affordable and high-quality innovative biologics to patients around the world.

About NCT05483530

This randomised， double-blind， multicentre phase 2 clinical study aims to evaluate the efficacy， safety， and tolerability of HLX53 in combination with HANSIZHUANG and HANBEITAI versus placebo in combination with HANSIZHUANG and HANBEITAI in previously untreated patients with locally advanced or metastatic hepatocellular carcinoma. The study consists of two parts. Part A is the safety run-in stage， which follows a “3+3” dose-escalation design. Eligible patients will be given different doses of HLX53 (1000 mg or 2000 mg) in combination with HANSIZHUANG (300 mg) and HANBEITAI (15 mg/kg) intravenously， every three weeks. Part B is the preliminary efficacy exploration stage. Eligible patients will be randomly assigned (1:1:1) to receive intravenous HLX53 (1000 mg)， HLX53 (2000 mg)， or placebo in combination with HANSIZHUANG (300 mg) and HANBEITAI (15 mg/kg)， every three weeks. The primary endpoints of Part A are safety and tolerance， evaluating the proportion of patients with a dose-limiting toxicity (DLT) event in each group. The primary endpoints of Part B are objective response rate and progression-free survival assessed by independent radiological review committee per RECIST v1.1.

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， 5 products have been launched in China， 3 have been approved for marketing in overseas markets， 23 indications are approved worldwide， and 3marketing applications have been accepted for review in China 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 backbone. Apart from the launched products 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) and HANBEITAI (bevacizumab)， the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours， squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC)， and esophageal squamous cell carcinoma (ESCC)， making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more， Henlius has conducted over 30 clinical studies for 16 products， expanding its presence in major markets as well as emerging markets.

(复星医药)【ATI-014】REAL WORLD 2 ゆりあ2004-08-26アタッカーズ&$in mad90分钟

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