March 26, 2026, Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in a Phase 1b/2 trial (HLX701-CRC201) evaluating its novel recombinant human SIRPα-Fc fusion protein, HLX701, in combination with cetuximab and chemotherapy in patients with advanced RAS/BRAF wild-type metastatic colorectal cancer (mCRC).
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. Standard first- and second-line treatments for advanced/metastatic colorectal cancer typically include fluoropyrimidine-based chemotherapy combined with either anti-angiogenic agents (anti-VEGF targeted therapy, e.g., bevacizumab) or anti-EGFR targeted therapy. Specifically, for patients with RAS/BRAF wild-type mCRC, cetuximab (anti-EGFR targeted agents) plus chemotherapy is one of the recommended first-line regimens. However, as the disease progresses to later lines, treatment options become more limited and increasingly depend on prior treatment response, performance status (e.g., ECOG score), and specific molecular subtypes3-4. Later-line options5-7 such as regorafenib, fruquintinib, and TAS-102 offer limited clinical overall benefits, underscoring a critical unmet need for more effective and combination-ready therapies. Immunotherapies targeting the CD47-SIRPα signaling pathway have entered clinical trials in colorectal cancer and other solid and hematologic malignancies. Notably, its combination regimens have shown potential synergy in specific molecular subtypes of cancer8-9. As next-generation CD47-SIRPα-targeted therapies continue to advance, further clinical validation is warranted to establish their efficacy and optimal combination strategies.
HLX701 is a next-generation SIRPα-Fc fusion protein in-licensed from FBD Biologics Limited (“FBD”), a subsidiary of HanchorBio, and is being advanced under a collaboration agreement between the parties. This molecule is an engineered fusion protein combining a human SIRPα immunoglobulin (IgV) domain with the crystallizable fragment (Fc) region of human Immunoglobulin G4 (IgG4). It binds to CD47 on tumor cells with high affinity, effectively blocking the inhibitory CD47 "don't eat me" signaling, thereby promoting macrophage-mediated phagocytosis of tumor cells and enhancing anti-tumor activity. It further activates T cells via antigen presentation, ultimately achieving synergistic engagement of both innate and adaptive immunity.
Notably, nonclinical and early clinical data suggest that HLX701, while binding selectively and with high affinity to tumor CD47, exhibits minimal binding to CD47 on normal cells such as red blood cells (RBCs). Consequently, it neither induces RBC agglutination nor promotes macrophage-mediated RBC phagocytosis, thereby demonstrating a lower potential to cause common hematological adverse events, including anemia and thrombocytopenia, in clinical settings. In animal models, HLX701 has shown additive or synergistic antitumor activity when combined with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor (EGFR) inhibitors, or anti-angiogenic agents across multiple tumor models, including colorectal, gastric, breast, and lung cancers. Currently, a Phase 1 dose-escalation study of HLX701 monotherapy is ongoing in both China and the U.S., and Ib/2a studies of HLX701 in combination with various agents are also underway in China.
Among them, the company's self-developed anti-PD-1 monoclonal antibody (mAb), serplulimab, is the world's first anti-PD-1 mAb approved for first-line treatment of small cell lung cancer (SCLC), and the first and only anti-PD-1 with positive results from a phase 3 registrational trial in the perioperative treatment of gastric cancer (GC). To date, it has been approved in over 40 countries and regions, including China, Germany, the UK, India, and Singapore. HLX43 is a potential best-in-class pan-tumor ADC targeting PD-L1 that integrates dual mechanisms: immune checkpoint blockade and payload-mediated cytotoxicity. It has shown broad therapeutic potential in preclinical and early clinical studies, with an encouraging safety profile and preliminary efficacy in non-small cell lung cancer (NSCLC), cervical cancer (CC), and esophageal squamous cell carcinoma (ESCC)， with ongoing validation in other solid tumors such as cervical cancer (CC) and esophageal squamous cell carcinoma (ESCC). HLX701 represents a key asset in Henlius' immuno-oncology pipeline. Its differentiated molecular design holds promise for an improved safety profile and the potential to synergize deeply with Henlius' existing pipeline assets, thereby paving the way for next-generation immuno-oncology treatment strategies.
Guided by unmet clinical needs and its antibody platform strength, Henlius will pursue novel targets with high potential, actively explore frontier technologies, and seek partnerships for premium, innovative assets to bring more quality, affordable treatment options to patients worldwide.
About HLX701-CRC201
This Phase 1b/2 clinical study compares HLX701 in combination with cetuximab and chemotherapy (FOLFOX/FOLFIRI) versus placebo in combination with cetuximab and chemotherapy (FOLFOX/FOLFIRI) in patients with recurrent, unresectable, or metastatic RAS/BRAF wild-type colorectal cancer who have previously received chemotherapy. This study consists of three stages: In Stage 1 (safety run-in), a 3+3 dose-escalation design is used, with a total of 4 dose levels ranging from 5 mg/kg to 18 mg/kg. Subjects will be treated with HLX701 in combination with cetuximab and chemotherapy at different dose levels, with intravenous administration once per week. In Stage 2, there are 3 dose groups ranging from 8 mg/kg to 18 mg/kg, administered once weekly by intravenous infusion, to evaluate the clinical efficacy and safety of HLX701 in combination with cetuximab and chemotherapy at different dose levels. Stage 3 is a randomized, double-blind, multi-center study comparing the efficacy and safety of HLX701 or placebo in combination with cetuximab and chemotherapy. The primary endpoint for Stage 1 is the proportion of dose-limiting toxicities (DLTs), while secondary endpoints include safety indicators such as adverse events, efficacy indicators such as objective response rate (ORR) and disease control rate (DCR), pharmacokinetic (PK) parameters, and immunogenicity. The primary endpoints for Stage 2 are determination of the recommended Phase 2 dose (RP2D) and the ORR and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). The primary endpoints for Stage 3 are the ORR and PFS as assessed by BICR. The secondary endpoints of Stage 2 and Stage 3 include safety indicators such as adverse events, efficacy endpoints (e.g., ORR and PFS assessed by investigators, overall survival [OS]), PK parameters, and immunogenicity, as well as the exploration of the association between biomarkers and efficacy.
References
1. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.
2. Han B, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53.
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Colon Cancer version 5.2025
4. 2025 CSCO结直肠癌诊疗指南
5. Grothey A, et al; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12.
6. Mayer R J, et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer[J]. New England Journal of Medicine, 2015, 372(20):1909-1919.
7. Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients with Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486–2496.
8. Eng C, et al. A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors. Target Oncol. 2025 May;20(3):519-530.
9. Lentz RW, et al. Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer. Cancer Res Commun. 2025 Nov 1;5(11):2039-2052.