February 11, 2026, Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in China in a Phase 1b/2 trial(HLX43-mCRC202), for the company's innovative programmed death-ligand 1 (PD-L1) antibody-drug conjugate (ADC), HLX43, in combination with serplulimab, an anti-PD-1 monoclonal antibody (mAb) or independently developed recombinant anti-EGFR mAb HLX07 in patients with advanced or metastatic colorectal cancer (mCRC). Henlius is vigorously advancing the clinical development of HLX43 globally, with its pan-tumor activity being explored across 10 clinical studies in various solid tumors, including non-small cell lung cancer(NSCLC), cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal carcinoma (NPC), mCRC, gastric or gastroesophageal junction (G/GEJ) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC).
Colorectal cancer is a highly prevalent malignancy both in China and globally. In 2022, there were approximately 1.926 million new cases and 904,000 deaths worldwide, with China accounting for 517,000 new cases and 240,000 deaths, ranking second in incidence and fourth in mortality among all cancers1-2. For patients with advanced or metastatic colorectal cancer, the first- and second-line standard treatments primarily involve chemotherapy regimens based on fluoropyrimidines combined with either anti-angiogenic agents (anti-VEGF targeted therapy, e.g., bevacizumab) or anti-EGFR targeted therapy. Specially, for patients with RAS/BRAF wild-type mCRC, combination therapy with anti-EGFR targeted agents like cetuximab is recommended. Patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) mCRC are more likely to benefit from PD-1 inhibitors. However, when the disease progresses to the third-line setting and beyond, treatment strategies become more limited and are highly dependent on the patient's prior treatment response, performance status (e.g., ECOG score), and specific molecular subtypes3-4. Current later-line treatment options for advanced colorectal cancer include oral targeted drugs such as regorafenib, fruquintinib, and TAS-1025-7 , as well as emerging combination strategies. Nonetheless, the clinical benefits for patients in later-line settings remain generally limited, highlighting an urgent unmet need for more effective treatment options.
HLX43 is a potentially best-in-class pan-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Compared to ADCs that target driver mutations, HLX43 engages the pan-tumor target PD-L1, demonstrating biomarker-independent and broad-spectrum anti-tumor potential. Its antibody backbone is derived from Henlius's proprietary anti-PD-L1 antibody, HLX20, ensuring high antigen binding and efficient tumor cell internalization. The cleavable linker-payload is licensed from MedLink’s TMALIN® platform, enables cytotoxic release both intracellularly post-internalization and within the tumor microenvironment. Currently, it has demonstrated manageable safety profile and encouraging efficacy in various solid tumors, with notable anti-tumor activity observed in various NSCLC patient subgroups. The company has enrolled more than 300 NSCLC patients globally(accounting for over 60% of the total enrolled population), with an international multicenter Phase 2 clinical trial for NSCLC (HLX43-NSCLC201) underway in countries including China, the United States, Japan, and Australia. In addition, phase 2 proof of concept (POC) data of HLX43 in CC and ESCC continue to emerge, providing compelling new evidence for its pan-tumor therapeutic potential. To further maximize the clinical value of the product, the company has simultaneously initiated multiple clinical trials evaluating HLX43 in combination with serplulimab, as well as with HLX07, for the treatment of advanced solid tumors.
HLX07 is an innovative anti-EGFR mAb developed by Henlius. Compared with cetuximab, HLX07 demonstrates lower immunogenicity and higher target affinity. Fc engineering extends its half-life, enabling every-3-week dosing that facilitates combination with other agents and promotes synergistic anti-tumor efficacy. The Phase 1b/2 clinical study of HLX07 in combination with chemotherapy for the treatment of advanced solid tumors demonstrated favorable safety and tolerability. Additionally, Phase 2 clinical trials evaluating HLX07 as a monotherapy or in combination with serplulimab for the treatment of solid tumors are currently underway. Serplulimab is the world’s first and only anti-PD-1 mAb to have succeeded in a phase 3 registration study for perioperative gastric cancer, to receive Breakthrough Therapy Designation from the CDE as well as being granted Priority Review for the treatment of this indication. Meanwhile, it is the first anti-PD-1 mAb approved for the first-line treatment of small cell lung cancer (SCLC). Up to date, serplulimab has been approved for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), ESCC, and non-squamous non-small cell lung cancer (nsqNSCLC). Meanwhile, an international multicenter Phase 3 clinical trial of serplulimab in combination with bevacizumab and chemotherapy as a first-line treatment for mCRC is in progress globally.
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 HLX43-mCRC202
This study is a phase 1b/2 clinical trial evaluating the safety, tolerability, and efficacy of HLX43 in combination with HLX07 or HANSIZHUANG in patients with advanced or metastatic colorectal cancer. The study consists of two parts. Part 1 includes Stage 1 (safety run-in) and Stage 2 (dose expansion). Stage 1 adopts a 3+3 dose‑escalation design, in which patients will receive HLX43 at 2.5 mg/kg or 3.0 mg/kg combined with a fixed dose of HLX07 (1000 mg), administered by intravenous infusion once every three weeks (Q3W). The primary objective of Stage 1 is to evaluate the safety and tolerability of different dose levels of HLX43 in combination with HLX07 in patients with advanced or metastatic colorectal cancer. Secondary objectives include assessment of the pharmacokinetic (PK) characteristics and immunogenicity of HLX43, evaluation of efficacy, potential pharmacodynamic effects, and potential predictive or resistance biomarkers. Stage 2 is a randomized, multicenter, open‑label study. HLX43 at two dose levels will be expanded in combination with a fixed dose of HLX07. Based on safety data from the Stage 1, the dose levels of HLX43 are preliminarily set at 2.5 mg/kg and 3.0 mg/kg. The primary objective of Stage 2 is to evaluate the efficacy of different doses of HLX43 in combination with fixed‑dose HLX07 in metastatic colorectal cancer (mCRC) patients. Secondary objectives include evaluation of safety and tolerability, the PK characteristics and immunogenicity of HLX43, and potential predictive or resistance biomarkers. Part 2 is a randomized, multicenter, open‑label study to evaluate the efficacy and safety of HLX43 at 2.0 mg/kg or 2.5 mg/kg in combination with a fixed dose of HANSIZHUANG (300 mg), Q3W, in patients with mCRC. The primary objective of Part 2 is to assess the efficacy of HLX43 in combination with HANSIZHUANG in mCRC patients. Secondary objectives include evaluation of safety and tolerability, the PK characteristics and immunogenicity of HLX43, and exploration of potential predictive or resistance biomarkers.
References
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