Shanghai, China, June, 3, 2025 – Shanghai Henlius Biotech, Inc. (2696. HK) announced the first release of results from the phase 1 clinical trial of HLX43, a PD-L1-targeting antibody-drug conjugate (ADC), for the treatment of advanced or metastatic solid tumors at the 2025 ASCO Annual Meeting. The leading principal investigator of this study is Jie Wang from the Cancer Hospital Chinese Academy of Medical Sciences. Leveraging on the precise molecular design and multiple innovative mechanisms, HLX43 has demonstrated superior anti-tumor activity with a manageable safety profile in patients with advanced/metastatic solid tumors. Particularly, encouraging preliminary efficacy was observed in non-small cell lung cancer (NSCLC) and thymic squamous cell carcinoma (TSCC) patients, demonstrating best-in-class potential for clinical development. At present, no PD-L1 targeting ADC has been approved for marketing globally. HLX43 may thus benefit more patients with advanced or metastatic solid tumors by providing a novel treatment option for those who are unresponsive or have developed resistance to PD-1/PD-L1-targeted therapies.

Initial Phase 1 Data Presentation: Favorable Safety Profile and Preliminary Antitumor Activity Observed, Especially in the NSCLC and TSCC Paients

The results presented at the 2025 ASCO Annual Meeting were from the phase 1 clinical study, which evaluated the safety, tolerability, and pharmacokinetic characteristics of HLX43 (Anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors. The results indicated that HLX43 was well tolerated with no new safety signals across different dose and exhibited encouraging preliminary efficacy in patients with advanced solid tumors, including those with NSCLC and TSCC, who had failed standard therapies, which warrants further investigation.

Study Design:

This study includes two parts. Phase 1a and 1b were a dose escalation and dose expansion phase, respectively, to explore different doses of HLX43. In phase 1a, patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors that were refractory to or could not receive standard therapies received intravenous HLX43 at 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 2.5 mg/kg, 3 mg/kg, or 4 mg/kg, Q3W. In phase 1b, patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard treatment received HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg, Q3W. The primary endpoints for phase 1a were the proportion of subjects experiencing dose-limiting toxicity (DLT) in each dose group within three weeks after the first administration of HLX43 and the maximum tolerable dose (MTD) while that for phase 1b were the recommended phase 2 (RP2D) dose and BICR-assessed objective response rate (ORR).

Results:

As of the data cut-off date Mar 28, 2025, a total of 21 patients were enrolled in phase 1a to receive HLX43 at 0.5 mg/kg (n=3), 1 mg/kg (n=3), 2 mg/kg (n=3), 2.5 mg/kg (n=3), 3 mg/kg (n=3), or 4 mg/kg (n=6). In phase 1b, 21 patients with NSCLC (15 [71.4%] had squamous type and 6 [28.6%] had nonsquamous) were enrolled to receive HLX43 at 2 mg/kg; enrolment of patients into the 2.5 and 3.0 mg/kg dose groups is ongoing. Hence, only the data from the 2.0 mg/kg group is presented here. Median follow-up duration was 9.7 months and 7.0 months for the two respective cohorts. The median prior lines of therapy for phase 1a and 1b patients were 2 and 3 respectively. All patients in phase 1b 2.0 mg/kg group received platinum-based treatment previously.

Median progression-free survival (PFS) was 4.2 months for the phase 1a cohorts and 5.4 months for phase 1b 2.0 mg/kg cohort. Median overall survival (OS) was 8.9 months and not reached, respectively.

All patients in the various dose groups experienced treatment-emergent adverse events (TEAEs) that were mostly grades 1-2. In phase 1a and 1b, the incidence rates of grade 3 or higher treatment-related adverse events (TRAEs) were 28.6% (n=21) and 42.9% (n=21), respectively. At 2.0 mg/kg dose level, HLX43 demonstrated low hematologic toxicity (anemia 14.3%, lymocyte count decreased 14.3%, platelet count decreased 0%, neutrophil count decreased 0%), supporting future expansion into 1L therapy and combination regimens.

Pan-Tumor Targeting ADC with Innovative Mechanisms of Action to Benefit Broad-spectrum Tumor Patients

HLX43 is a novel PD-L1-targeting ADC, composed of a fully humanized anti-PD-L1 IgG1 antibody, a novel tripeptide linker and topoisomerase inhibitor payload. The drug-to-antibody ratio (DAR) is around 8. Its mechanisms of action integrate targeted cytotoxic delivery and immune checkpoint activation through PD-L1/PD-1 blockade. Upon binding to PD-L1-expressing tumor cells, HLX43's cytotoxic payload can be delivered into tumor cells via dual mechanisms—First, the ADC undergoes receptor-mediated endocytosis, releasing the cytotoxic payload intracellularly via linker cleavage, and the payload further diffuses into neighboring tumor cells via bystander effect, thereby blocking DNA replication and triggering tumor cell apoptosis. Meanwhile, the anti-PD-L1 antibody of HLX43 activates immune modulation and blocks immune checkpoints, driving synergistic antitumor efficacy. Preclinical and phase 1 studies have demonstrated that, HLX43 has a favorable safety profile and exhibits potent anti-tumor activity.

HLX43 is the leading PD-L1-targeting ADCs that is progressing to clinical development globally. It has received investigational new drug (IND) approvals from the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA). Currently, HLX43 is being investigated in phase 2 clinical trials for a variety of solid tumor indications including NSCLC, TSCC, HCC, ESCC, HNSCC, CC and NPC. Both monotherapy studies and a phase 1b/2 trial combining HLX43 with serplulimab (HANSIZHUANG, Henlius’ proprietary anti-PD-1 monoclonal antibody) are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and immunotherapy-induced immune activation.