On September 9, 2025, Henlius (2696.HK) announced that updated results from the phase 2 dose-finding study of HLX07, a recombinant anti-EGFR monoclonal antibody (mAb), independently developed by the company, in combination with the anti-PD-1 mAb serplulimab and chemotherapy as first-line treatment for patients with EGFR overexpression advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) were presented at the 2025 World Conference on Lung Cancer (WCLC).
A large EGFR overexpression population with urgent clinical needs
Among patients with NSCLC worldwide, the prevalence of EGFR overexpression is approximately 40%–89% (varying by histology, ethnicity, and other factors), representing millions of newly diagnosed patients annually [1-3]. Notably, up to 89% of sqNSCLC patients present with EGFR overexpression[1-2]. Despite the widespread use of PD-(L)1 inhibitors in first-line advanced or metastatic sqNSCLC, no validated first-line regimen specifically addresses the EGFR overexpression population, underscoring the need for innovative strategies.
Dual-target synergy: complementary advantages
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 immuno-oncology agents. Preclinical studies showed synergistic antitumor activity of HLX07 with serplulimab across tumor models[4].
Serplulimab is the world’s first anti-PD-1 monoclonal antibody approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). To date, it has benefited over 120,000 patients and covered nearly half of the global population. The combination of HLX07 and serplulimab blocks EGFR signaling while activating immune responses, supporting strong therapeutic synergy.
Positive efficacy with manageable safety
The HLX10HLX07-sqNSCLC-201 trial is a randomized, multicenter phase 2 dose-finding study evaluating multiple regimens of HLX07 (different doses), serplulimab, and chemotherapy. Part 3 assessed the preliminary efficacy of the triplet therapy in first-line, EGFR high-expressing (H-score ≥150) sqNSCLC with no prior systemic therapy. Patients were randomized 1:1 to HLX07 800 mg or 1000 mg (IV, q3w) plus serplulimab 300 mg and chemotherapy.
According to the updated results, the combination of HLX07 with serplulimab and chemotherapy demonstrated remarkable antitumor activity and durable efficacy in patients with EGFR overexpression sqNSCLC. At a median follow-up of 18.6 months, both dose groups achieved an objective response rate (ORR) of around 70% and a disease control rate (DCR) of over 90%. The median progression-free survival (PFS) reached 17.4 months in the high-dose group, while the median PFS of the low-dose group was not reached at the time of follow-up. The median overall survival (mOS) and median duration of response (mDOR) were not reached in either group, indicating sustained efficacy with potential for further improvement. Most treatment-emergent adverse events (TEAEs), such as rash, were manageable, reflecting a favorable safety profile.
Detailed Findings
As of 5 March 2025, 27 patients were enrolled and randomized to group A (n=13; HLX07 800 mg) or group B (n=14; HLX07 1000 mg). Fifteen (55.6%) had metastatic sqNSCLC. The median follow-up was 18.6 months.
Confirmed ORR per RECIST 1.1 was 69.2% (95% CI 38.6–90.9) in group A and 71.4% (95% CI 41.9–91.6) in group B; DCR was 92.3% (95% CI 64.0–99.8) and 100% (95% CI 76.8–100.0), respectively.
The median PFS was not reached in (95% CI 4.1–not evaluable [NE]) in group A and 17.4 months (95% CI 8.1–NE) in group B.
As of data cutoff date, mOS and mDOR were not reached in either group.
All patients reported treatment-emergent adverse events (TEAEs). The most common grade ≥3 TEAEs included skin reactions and electrolyte abnormalities; no new safety signals were identified compared with agents of the same class.
Continued commitment to lung cancer innovation
Building on serplulimab’s leadership in SCLC immunotherapy, Henlius is expanding a diversified lung-cancer pipeline, including HLX43 and HLX07, to address distinct molecular segments in NSCLC. The positive dose-finding phase 2 signals support the feasibility of combining EGFR-targeted therapy with immunotherapy and lay the groundwork for larger-scale studies in the EGFR overexpression sqNSCLC population.
