Henlius Biotech Initiates Phase Ib/II Study for HLX43 ADC Combinations in Colorectal Cancer

Shanghai Henlius Biotech, Inc. (HKG: 2696) announced first patient dosing in a Phase Ib/II clinical study evaluating HLX43, a PD-L1-targeting antibody-drug conjugate (ADC), in combination with HLX07 (anti-EGFR mAb) or HanSiZhuang (serplulimab, PD-1 mAb) for advanced or metastatic colorectal cancer (CRC). The trial marks Henlius’s entry into ADC-based immuno-oncology combinations, leveraging its self-developed antibody platforms and licensed toxin-linker technology.

Clinical Trial Design

ElementDetail
CompanyShanghai Henlius Biotech, Inc. (HKG: 2696)
AssetsHLX43 (PD-L1 ADC) + HLX07 (anti-EGFR mAb) OR HanSiZhuang (PD-1 mAb)
IndicationAdvanced/metastatic colorectal cancer (mCRC)
Study PhasePhase Ib/II
Study StructurePart 1: Safety run-in + dose expansion; Part 2: Randomized efficacy evaluation
Part 2 DesignHLX43 (2.0 or 2.5 mg/kg) + HanSiZhuang (300 mg Q3W) vs. comparator

Product Profile & Mechanism

AssetClassMechanismOrigin
HLX43PD-L1-targeting ADCPD-L1 antibody + DNA topoisomerase I inhibitor toxinLicensed-in ADC technology + self-developed PD-L1 antibody
HLX07Anti-EGFR monoclonal antibodyEGFR pathway blockadeIn-house developed
HanSiZhuang (serplulimab)PD-1 monoclonal antibodyImmune checkpoint inhibitionSelf-developed; approved in China for 4 indications (sqNSCLC, ES-SCLC, ESCC, nsqNSCLC)

Strategic Rationale & Combination Logic

CombinationRationaleStrategic Value
HLX43 + HLX07PD-L1 ADC + EGFR blockadeDual targeting of immune evasion and growth signaling; potential for RAS wild-type CRC population
HLX43 + HanSiZhuangPD-L1 ADC + PD-1 mAbDual PD-L1/PD-1 axis inhibition with cytotoxic payload; addresses primary and acquired resistance to checkpoint monotherapy

Study Objectives & Biomarker Strategy

Endpoint CategorySpecific AssessmentsInnovation Focus
Safety/TolerabilityDose-limiting toxicities; MTD determinationADC + immunotherapy combination safety profile
EfficacyORR, DOR, PFS, OS (Part 2 randomized)PD-L1 ADC mechanism validation in MSS CRC (typically immunotherapy-resistant)
PharmacokineticsHLX43 exposure; immunogenicityADC PK optimization for combination setting
BiomarkersPredictive/resistance markersPatient selection strategy for Phase III design

Market Context & Competitive Positioning

FactorStrategic Analysis
CRC Immunotherapy Challenge95% of mCRC is MSS (microsatellite stable)resistant to PD-1 monotherapy; ADC + IO combinations represent novel approach to overcome resistance
Henlius Portfolio SynergyHanSiZhuang commercial infrastructure (4 approved indications) enables rapid CRC trial enrollment and combination therapy expertise
ADC Competitive LandscapeT-DXd (Enhertu), sacituzumab govitecan (Trodelvy) lead in solid tumors; HLX43 PD-L1 targeting offers differentiation vs. HER2/TROP2 ADCs
China CRC Market>380,000 new cases annually; limited targeted therapy options beyond anti-EGFR (RAS wild-type); significant unmet need in RAS-mutant population
Global PotentialMSS CRC represents largest immunotherapy-resistant population globally; China-first data supports US/EU partnership discussions

Forward‑Looking Statements
This brief contains forward‑looking statements regarding HLX43 clinical development in colorectal cancer, combination therapy efficacy in MSS tumors, and Henlius Biotech’s ADC platform validation. Actual results may differ due to Phase Ib/II safety outcomes, competitive dynamics with established ADCs, and biomarker discovery success.-Fineline Info & Tech