HENLIUS (02696) has announced that the first patient in China (excluding Hong Kong, Macau, and Taiwan) has been dosed in a Phase 1b/2 clinical study evaluating HLX701, a recombinant human SIRPα-IgG4 Fc fusion protein injection, in combination with cetuximab and chemotherapy for the treatment of advanced colorectal cancer.
This study is a Phase 1b/2 clinical trial comparing HLX701 plus cetuximab and chemotherapy (FOLFOX/FOLFIRI) against a placebo plus cetuximab and chemotherapy (FOLFOX/FOLFIRI) in patients with recurrent, unresectable, or metastatic RAS/BRAF wild-type colorectal cancer who have previously received chemotherapy. The trial consists of three phases. The first phase is a safety run-in period utilizing a 3+3 dose escalation design across four dose groups ranging from 5 mg/kg to 18 mg/kg. Patients will receive HLX701 in combination with cetuximab and chemotherapy via intravenous infusion once a week.
The second phase involves three dose groups from 8 mg/kg to 18 mg/kg, also administered weekly, and aims to evaluate the clinical efficacy and safety of the combination therapy at different dose levels. The third phase is a randomized, double-blind, multicenter study designed to compare the efficacy and safety of HLX701 versus a placebo, each combined with cetuximab and chemotherapy.
The primary endpoint for the first phase is the assessment of the incidence of dose-limiting toxicities (DLT). Secondary endpoints include safety indicators such as adverse events, efficacy measures like objective response rate (ORR) and disease control rate (DCR), pharmacokinetic (PK) parameters, and immunogenicity. The primary endpoints for the second phase are to explore the recommended Phase 2 dose (RP2D), and ORR and progression-free survival (PFS) as assessed by a Blinded Independent Central Review (BICR). The primary endpoints for the third phase are BICR-assessed ORR and PFS. Secondary endpoints for the second and third phases include safety indicators, overall survival (OS), investigator-assessed ORR and PFS, PK parameters, immunogenicity, and an exploration of the correlation between biomarkers and efficacy.
HLX701 is a SIRPα-Fc fusion protein licensed by the company from FBD Biologics Limited and is intended for the treatment of various advanced solid tumors. Multiple Phase 1/2 clinical trials for this product are currently underway globally. Under the licensing agreement, HENLIUS holds exclusive rights to develop, manufacture, and commercialize HLX701 in China (excluding Taiwan) and specific countries in Southeast Asia, the Middle East, and North Africa.
HLX701 is an engineered fusion protein combining a modified human SIRPα immunoglobulin (IgV) domain with a human immunoglobulin G4 (IgG4) Fc region. By binding to CD47 on tumor cells, HLX701 effectively blocks the inhibitory CD47 "don't eat me" signal, promoting macrophage-mediated phagocytosis of tumor cells and enhancing anti-tumor activity. Preclinical studies have shown that HLX701 can produce synergistic effects with various agents, including chemotherapeutics, immune checkpoint inhibitors, EGFR inhibitors, and anti-angiogenic drugs, suggesting its potential to synergistically enhance both innate and adaptive immune responses when combined with standard treatment regimens.
In January 2026, the Investigational New Drug (IND) application for this Phase 1b/2 clinical trial of HLX701 in combination with cetuximab and chemotherapy for advanced colorectal cancer was approved by the National Medical Products Administration (NMPA). As of the date of this announcement, no CD47-targeting SIRPα-Fc fusion protein has been approved for marketing anywhere in the world.
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