入選 ESMO Asia優選論文口頭報告｜復星醫藥子公司復宏漢霖PD-L1 ADC HLX43...

（來源：復星醫藥）

轉自：復星醫藥

• 繼肺癌、胸腺癌后，HLX43廣譜抗腫瘤潛力持續驗證

• 入選ESMO Asia優選論文口頭報告，HLX43晚期宮頸癌II期臨床數據首發亮相

• 初步臨床療效優異且安全性可控，總人群ORR、DCR分別為41.4%及82.8%，其中3mg/kg劑量組ORR和DCR高達70.0%和100%

2025年12月5日，在2025年歐洲腫瘤內科學會亞洲年會（ESMO Asia）上，復星醫藥子公司復宏漢霖PD-L1 ADC HLX43用于復發/轉移性宮頸癌的II期臨床研究數據以優選論文口頭報告形式首發亮相，展現了令人鼓舞的初步療效，繼非小細胞肺癌、胸腺癌之后，再度印證了該產品在實體瘤領域的廣譜治療潛力。

宮頸癌數據報捷，廣譜潛力再驗證

宮頸癌（CC）、卵巢癌等婦科惡性腫瘤給女性健康造成了嚴重威脅 [1-2]，尤其晚期患者預后較差。一線聯合療法治療后，約30%的晚期宮頸癌患者出現疾病復發[3]，其5年生存率約為17%[4]，包含多西他賽在內的二線化療客觀緩解率（ORR）僅約為13.2%[5]，盡管PD-1抑制劑及靶向組織因子（TF）的抗體偶聯藥物（ADC）Tisotumab vedotin已獲批上市，但其治療既往治療失敗的復發轉移性宮頸癌療效也有限，ORR多不到18%[6-9]，亟需更高效、臨床獲益更為顯著的治療新選擇。

本次發布基于一項開放、隨機、多中心的II期臨床研究，由山東省腫瘤醫院于金明院士牽頭開展。經組織學確診為復發/晚期宮頸癌（CC）且既往接受過標準一線治療失敗、不耐受或禁忌的患者，按1:1:1比例隨機分組，每3周接受一次劑量為2 mg/kg、2.5 mg/kg或3 mg/kg的HLX43治療。主要終點為研究者根據RECIST v1.1評估的客觀緩解率（ORR）和無進展生存期（PFS）。次要終點包括其他有效性指標、安全性、藥代動力學、免疫原性和生物標志物探索。

截至2025年9月1日，本研究共納入30例患者，隨機分配接受劑量為2 mg/kg（n=10）、2.5 mg/kg（n=10）和3 mg/kg（n=10）的HLX43治療。其中超過80%的患者PD-L1綜合陽性評分（CPS）≥1。 患者既往接受腫瘤治療的中位線數為2.0（范圍1–4線）。全部患者接受過鉑類藥物化療，60%的患者接受過靶向治療，約50%患者接受過免疫治療，中位隨訪時間為3.5個月。

在29例可評估療效的患者中，研究者評估的客觀緩解率（ORR）為41.4%，疾病控制率（DCR）為82.8%。其中，3 mg/kg劑量組的ORR和DCR為70.0%和100%，患者中位PFS尚未達到。

亞組分析顯示，HLX43在CPS≥1的PD-L1陽性晚期宮頸癌患者中初步療效優異，ORR和DCR分別達到 45.8%和 87.5%，并在CPS＜1的PD-L1陰性患者中展現了一定療效（1例2mg/kg劑量組患者達到PR），但鑒于此次納入的患者基數較小，且CPS ≥ 1占比較高（超過80%），仍需待后續更大樣本量的隨機對照研究，以明確HLX43在PD-L1陰性亞組中的確切療效。

安全性方面，18列（60.0%）患者報告了≥3級治療相關不良事件，主要為可管理的血液學毒性，常見包括為中性粒細胞計數降低（30.0%）、貧血（30.0%）和淋巴細胞計數降低（ 23.3%），6例（20.0%）患者因TRAE導致劑量減少，無TRAE導致的患者停止治療（導致停藥的TRAE發生率為0%），且無TRAE導致的死亡。其中，7例（23.3%）患者發生免疫相關不良事件（irAE），主要包括甲狀腺功能減退癥等內分泌異常、皮疹等。無患者報告≥3級免疫相關不良事件（irAE），提示了HLX43的IO療效，且免疫相關毒性溫和，具有可控的安全性特征。

整體來看，HLX43 在復發/晚期宮頸癌（CC）的后線治療中展現出可控的安全性和令人鼓舞的初步療效，尤其在3.0 mg/kg 劑量下療效更為顯著，值得進一步研究。

肺癌療效優異，重磅實力定基石

HLX43是一款潛在同類最優及疾病領域最優的廣譜抗腫瘤ADC，兼具免疫檢查點阻斷與載荷細胞毒性的雙重作用機制。臨床前研究顯示，HLX43在PD-1/PD-L1單抗耐藥的非小細胞肺癌、宮頸癌、食管鱗癌等多個瘤種中展現出治療潛力，且耐受性良好。其I期臨床數據于2025美國臨床腫瘤學會（ASCO）年會及2025 世界肺癌大會（WCLC）上先后發布，在NSCLC等實體瘤中展現出“高效、低毒”的顯著療效，尤其在NSCLC的治療上，HLX43展現了全人群覆蓋的潛力，對于鱗狀/非鱗狀NSCLC，有無EGFR突變、有無腦轉移、PD-L1陽性/陰性的NSCLC患者人群都具有療效，不依賴生物標志物篩選。

目前，公司正全力推進HLX43臨床開發進程，在全球入組超過500例患者，其中NSCLC患者超過270例。隨著這一適應癥的后線療效逐步得到驗證，未來公司計劃開展更多HLX43在肺癌領域的III期臨床研究，全面覆蓋HLX43頭對頭對比多西他賽的二線臨床研究、HLX43用于NSCLC的一線治療及新輔助治療方案等。同時，HLX43作為全球首個布局胸腺癌的PD-L1 ADC，其國際多中心臨床研究在中、美、澳等國家同步推進。2025年10月，基于HLX43在胸腺癌后線治療中優異的初步療效，該產品獲得FDA孤兒藥資格認定，有望填補這一罕見高侵襲癌種 ADC治療的空白。

肺癌和胸腺癌之外，復宏漢霖已累計開展約10項HLX43治療多項實體瘤中的臨床研究，廣泛覆蓋宮頸癌等晚期婦科腫瘤、食管鱗癌、頭頸鱗癌、鼻咽癌、結直腸癌、胃癌/胃食管交界部癌、胰腺導管腺癌、肝細胞癌等。其中，HLX43在食管癌、鼻咽癌、胃癌等實體瘤中的概念驗證數據也將在ASCO GI、ASCO、ESMO等大會上陸續讀出。單藥之外，基于HLX43展現出的IO療效，公司積極探索HLX43與其他多元分子如公司自研創新抗EGFR單抗HLX07的聯合治療潛力，不斷挖掘和最大化該產品在臨床中的應用價值。

未來，復宏漢霖將持續聚焦患者未滿足的臨床需求，立足于HLX43等核心創新管線，不斷放大產品的差異化治療潛力，加速推動更大臨床價值的釋放，為全球患者帶來更具突破療效的治療方案。

【參考文獻】

[1] Siegel RL，Giaquinto AN，Jemal A.Cancer statistics，2024.CA Cancer J Clin.2024;74(1):12-49.doi:10.3322/caac.21820

[2] Han B，Zheng R，Zeng H，et al.Cancer incidence and mortality in China，2022.J Natl Cancer Cent.2024;4(1):47-53. Published 2024 Feb 2.doi:10.1016/j.jncc.2024.01.006

[3] Gennigens C, et al. Expert Rev Anticancer Ther. 2021 Jun;21(6):657-671.

[4] Marret G, et al. Expert Opin Biol Ther. 2019 Sep;19(9):871-877.

[5] McLachlan J, et al. Clin Oncol (R Coll Radiol). 2017 Mar;29(3):153-160.

[6] Chung, H. C. et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J. Clin. Oncol. 37, 1470–1478 (2019).

[7] Tewari, K. S. et al. Survival with cemiplimab in recurrent cervical cancer. N. Engl. J. Med. 386, 544–555 (2022).

[8] Naumann, R. W. et al. Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: results from the phase I/II checkMate 358 trial. J. Clin.Oncol. 37, 2825–2834 (2019).

[9] Vergote I, et al. NEJM. 2024 Jul; 391(1):44-55. ADC, antibody-drug conjugate; CC, cervical cancer; DAR, drug-antibody ratio; mPFS, median progression-free survival; ORR, objective response rate; PD-L1, programmed cell death-ligand 1; TME, tumour microenvironment; Top1, topoisomerase 1.

關于復宏漢霖

復宏漢霖（2696.HK）是一家國際化的創新生物制藥公司，致力于為全球患者提供可負擔的高品質生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已在全球獲批上市10款產品，4個上市申請分別獲中國藥監局和歐盟EMA受理。自2010年成立以來，復宏漢霖已建成一體化生物制藥平臺，高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。公司已建立完善高效的全球創新中心，按照國際藥品生產質量管理規范（GMP）標準進行生產和質量管控，不斷夯實一體化綜合生產平臺，其中，公司商業化生產基地已相繼獲得中國、歐盟和美國GMP認證。

復宏漢霖前瞻性布局了一個多元化、高質量的產品管線，涵蓋約50個分子，并全面推進基于自有抗PD-1單抗H藥 漢斯狀?的腫瘤免疫聯合療法。截至目前，公司已獲批上市產品包括全球首個獲批一線治療小細胞肺癌的抗PD-1單抗漢斯狀?（斯魯利單抗，歐洲商品名：Hetronifly?）、自主研發的中美歐三地獲批單抗生物類似藥漢曲優?（曲妥珠單抗，美國商品名：HERCESSI?，歐洲商品名：Zercepac?）、國內首個生物類似藥漢利康?（利妥昔單抗）、地舒單抗生物類似藥Bildyos?和Bilprevda?，以及帕妥珠單抗POHERDY?。公司亦同步就19個產品在全球范圍內開展30多項臨床試驗，對外授權全面覆蓋歐美主流生物藥市場和眾多新興市場。

Henlius' PD-L1 ADC HLX43 Cervical Cancer Data Debuts as Proffered Paper at 2025 ESMO Asia

• The encouraging efficacy observed across multiple solid tumors corroborates the broad-spectrum anti-tumor potential of HLX43

• Phase 2 clinical data of HLX43 in advanced cervical cancer presented in Proffered Paper Session at the 2025 ESMO Asia

• Encouraging preliminary efficacy was observed, with an ORR of 41.4% and DCR of 82.8% in the overall population, rising to 70.0% and 100% in the 3 mg/kg group, alongside a manageable safety profile

Shanghai, China, December 5, 2025—Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the results from a phase 2 proof of concept (POC) study of Henlius’ PD-L1 antibody-drug conjugate (ADC) HLX43 in recurrent/metastatic cervical cancer were first presented in Proffered Paper Session at the 2025 ESMO Asia Congress. The results demonstrated encouraging antitumor activity, providing further evidence of its broad-spectrum antitumor activity, previously observed in non-small cell lung cancer and thymic carcinoma.

Promising CC Data Add to Growing Evidence for Broad-Spectrum Potential

Cervical cancer (CC) and other gynaecological cancer pose a serious threat to women's health [1-2], particularly with poor prognosis in advanced-stage patients. Approximately 30% of advanced CC patients experience disease recurrence after first-line combination therapy [3], with a 5-year survival rate of about 17% [4]. The objective response rate (ORR) of second-line chemotherapy, including docetaxel, is only around 13.2% [5]. Although PD-1 inhibitors and the tissue factor (TF)-targeting antibody-drug conjugate (ADC) tisotumab vedotin have been approved, their efficacy in recurrent/metastatic CC after prior treatment remains limited, with ORR typically below 18% [6-9]. There is an urgent need for more effective therapeutic options with greater clinical benefits.

This open-label, randomised, multicentre phase 2 study was led by Academician Jinming Yu from the Shandong Cancer Hospital. Patients with histologically confirmed recurrent/metastatic CC who had previously failed, intolerant to, or contraindicated for standard first-line therapy were randomised 1:1:1 to receive HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg every 3 weeks. The primary endpoints were investigator-assessed objective response rate (ORR) and progression-free survival per RECIST v1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and biomarker explorations.

By the data cutoff date of September 1, 2025, 30 patients were enrolled and randomized to receive HLX43 at 2 mg/kg (n=10), 2.5 mg/kg (n=10) and 3 mg/kg (n=10). Over 80% of the patients had a PD-L1 combined positive score ≥ 1. The median line of prior antitumor therapy was 2.0 (range, 1–4). All patients received platinum-based chemotherapy, 60% received targeted therapy, approximately 50% received immunotherapy, and the median follow-up time was 3.5 months.

Among the 29 response evaluable patients, investigator-assessed ORR was 41.4% and disease control rate (DCR) was 82.8%. ORR, and DCR for the 3 mg/kg dose group was 70.0%, and 100%, respectively. The median Progression-Free Survival (PFS) has not yet been reached.

Subgroup analysis demonstrated that HLX43 exhibited promising preliminary efficacy in PD-L1 positivive(CPS≥1) advanced cervical cancer patients, with an ORR of 45.8% and a DCR of 87.5%, respectively. Notably, a signal of efficacy was also observed in PD-L1 negative (CPS <1) patients, with one patient in the 2 mg/kg dose group achieving partial response (PR). However, as the sample size of this study was limited and the population predominantly consisted of PD-L1 positive patients (>80%), these findings are preliminary. Further investigation in larger, randomized controlled trials is required to adequately characterize the efficacy of HLX43 in the PD-L1 negative subgroup.

In terms of safety, grade ≥3 treatment-related adverse events were reported in 18 (60.0%) patients, most commonly neutrophil count decreased (30.0%), anemia(30.0%) and lymphocyte count decreased (23.3%). Dose reductions due to TRAEs were reported in 6 patients (20.0%), with no TRAE-related treatment discontinuations and TRAE-related death. Immune-related adverse events were observed in 7 (23.3%) patients, primarily including endocrine disorder and rash. No grade 3 or higher immune-related adverse events (irAEs) were reported. This finding is supportive of an immunomodulatory mechanism of action for HLX43 and indicates a manageable and favorable immune-related safety profile.

HLX43, particularly at 3 mg/kg, exhibited promising efficacy and manageable safety in patients with previously treated recurrent/metastatic CC. Further investigation of HLX43 is warranted.

Compelling Efficacy in Lung Cancer Lays Foundation for Blockbuster Profile

HLX43 is a potential best-in-class as well best-in-disease broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data has shown that, HLX43 has good anti-tumor effects and a favorable tolerability profile in NSCLC, cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. The results from the phase 1 clinical trial of HLX43 were released at the 2025 ASCO Annual Meeting and 2025 WCLC, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain metastasis, and PD-L1 positive or negative patients.

The company is currently accelerating the clinical development of HLX43. To date, over 500 patients enrolled globally for HLX43, including more than 270 patients with NSCLC. With its efficacy in later-line NSCLC being validated, Henlius plans to initiate additional Phase 3 clinical studies for HLX43 in lung cancer. These trials will encompass a second-line, head-to-head study comparing HLX43 against docetaxel, as well as explorations in first-line treatment and neoadjuvant therapy regimens. Meanwhile, as the first PD-L1 ADC developed for thymic carcinoma globally, HLX43 is advancing its international multi-center clinical trials concurrently in China, the U.S., Australia, etc. In October 2025, based on the compelling preliminary efficacy data from later-line settings in thymic carcinoma (TC), the U.S. FDA granted Orphan Drug Designation (ODD) to HLX43 for the treatment of Thymic epithelial tumors (TETs), highlighting the drug's potential to address the significant unmet need for ADC therapies in this disease.

In addition to NSCLC and TC, Henlius is actively exploring HLX43's therapeutic potential in various solid tumors. The company has initiated about 10 clinical studies for HLX43, covering CC, ESCC, head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC). Proof-of-concept (PoC) results in ESCC, NPC and G/GEJ are also expected to be released on the upcoming international academic conferences including the ASCO Gastrointestinal (GI) Cancers Symposium, ASCO and ESMO. Building on its intrinsic immuno-oncology (IO) activity, Henlius is exploring combination therapies, such as with the in-house anti-EGFR antibody HLX07, to maximize HLX43's clinical value.

Guided by its commitment to address unmet medical needs, Henlius will continue to advance its core pipeline including HLX43 to deepen the differentiated therapeutic potential of our products, accelerate the delivery of greater clinical value, and ultimately deliver more breakthrough treatment options 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. To date, 10 products have been approved for marketing across multiple countries and regions, and 4 marketing 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 about 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 HANSIZHUANG (serplulimab, trade name: Hetronifly? in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, HANQUYOU (trastuzumab, trade name: HERCESSI? in the U.S., Zercepac? in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANLIKANG (rituximab), the first China-developed biosimilar, denosumab Bildyos? and Bilprevda?, and pertuzumab Poherdy?. What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.

To learn more about Henlius, visit https://www.henlius.com/en/index.html and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.