Henlius (2696.HK) today announced that a randomized, double-blind, multicentre, parallel-controlled Phase 2/3 clinical trial evaluating its self-developed recombinant anti-EGFR mAb pimurutamab (HLX07) in combination with the anti-PD-1 mAb serplulimab (trade name: Hetronifly® in Europe) and chemotherapy for the first-line treatment of patients with advanced squamous non-small cell lung cancer (sqNSCLC) has completed Clinical Trial Notification (CTN) in Australia, marking a crucial step in exploring innovative treatments for first-line treatment of sqNSCLC.
Addressing Unmet Needs in sqNSCLC: Clinical Potential of EGFR Overexpression
Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and comprises both squamous and non-squamous subtypes.¹ Squamous NSCLC (sqNSCLC) represents approximately 20%–30% of NSCLC cases and is generally associated with poorer clinical outcomes compared with non-squamous disease.² Epidermal growth factor receptor (EGFR) is widely overexpressed across multiple solid tumours, including both squamous and non-squamous NSCLC, and is considered a key driver of tumour initiation, progression, and treatment resistance.³ Globally, EGFR overexpression has been reported in approximately 40%–89% of patients with NSCLC, depending on histological subtype and ethnic background, suggesting that millions of newly diagnosed patients each year may fall within this population.⁴⁻⁶ Among patients with sqNSCLC, the prevalence of EGFR overexpression is even higher, approaching 90%.⁴⁻⁵ Given the widespread expression of EGFR in this population, the exploration of EGFR pathway–based combination strategies as first-line treatment approaches for the broader sqNSCLC population is supported by strong biological rationale and meaningful clinical investigational value.
It is noteworthy that EGFR overexpression is distinct from EGFR sensitizing mutations, with relatively low correlation between the two.⁷ In particular, classical sensitizing EGFR mutations are rare among patients with sqNSCLC.⁸ As a result, the majority of patients with EGFR-overexpressing squamous tumours do not harbour sensitizing EGFR mutations and are therefore unlikely to benefit from EGFR tyrosine kinase inhibitors (TKIs).⁸ Previous studies have demonstrated that anti-EGFR mAbs in combination with chemotherapy may provide clinical benefit in the treatment of squamous malignancies, including squamous NSCLC.⁹⁻¹⁰ In recent years, immunotherapy-based regimens combining PD-1/PD-L1 inhibitors with chemotherapy have significantly improved first-line treatment outcomes for patients with advanced sqNSCLC and have become one of the current standards of care.¹¹⁻²⁰ However, despite advances achieved with both targeted therapy–chemotherapy combinations and immunotherapy–chemotherapy regimens, overall efficacy gains remain limited¹¹⁻²¹, highlighting an urgent need for novel therapeutic strategies to further improve treatment outcomes and extend the durability of clinical benefit.
A Targeted and Immunotherapy Combination Strategy with Promising Clinical Activity
Pimurutamab is a humanized anti-EGFR mAb developed by Henlius, featuring reduced immunogenicity and enhanced binding affinity to the EGFR target. Through Fc engineering, pimurutamab demonstrates a significantly prolonged half-life, and the 3-week dosing frequency makes it more suitable for clinical use in combination with immunotherapies. Preclinical trials have shown that, compared with existing anti-EGFR mAbs, pimurutamab exhibits improved biological activity, significantly inhibiting tumour cell growth across multiple tumour models and demonstrating strong synergistic effects when combined with serplulimab.²² The combination not only blocks EGFR-mediated proliferative signalling but also simultaneously enhances antitumor immune responses, highlighting its promising potential as a synergistic combination therapy.
Positive results have been reported from a Phase 2 dose-exploration trial (HLX07-sqNSCLC-201) evaluating pimurutamab in combination with serplulimab and chemotherapy as a first-line treatment for patients with EGFR-overexpressing advanced or metastatic sqNSCLC. Updated data with median follow-up durations of 18.6 months and 23.5 months were successively presented at the 2025 World Conference on Lung Cancer (WCLC) and the International Summit on Frontiers and Innovations in Lung Cancer held in November 2025. Based on the latest analysis with a median follow-up of 23.5 months, the regimen demonstrated stable and durable antitumor activity across both dose cohorts, with an objective response rate (ORR) of approximately 70% and a disease control rate (DCR) exceeding 90%. In the high-dose cohort, median progression-free survival (mPFS) reached 17.4 months, while mPFS in the low-dose cohort had not yet been reached at the time of analysis. Median overall survival (mOS) and median duration of response (mDOR) remained immature in both cohorts. The overall safety profile was manageable, with no new safety signals observed.
This study (HLX07-sqNSCLC-301) is a randomized, double-blind, multicentre, parallel-controlled Phase 2/3 clinical study designed to evaluate pimurutamab in combination with serplulimab and chemotherapy versus placebo in combination with serplulimab or pembrolizumab and chemotherapy as first-line treatment in patients with advanced sqNSCLC. The study consists of two parts. Part I is a Phase 2 study, in which participants will be randomized in a 1:1:1 ratio to one of the three groups: Group A: pimurutamab 1000 mg in combination with serplulimab and chemotherapy; Group B: pimurutamab 600 mg in combination with serplulimab and chemotherapy; and Group C: placebo in combination with serplulimab and chemotherapy. Treatment will be administered once every 3 weeks (Q3W) for a total of 4 cycles, followed by maintenance therapy with the corresponding dose of pimurutamab or placebo in combination with serplulimab. The primary endpoints of Part I are progression-free survival (PFS) and objective response rate (ORR), as assessed by Blinded Independent Central Review (BICR). Part II is a Phase 3 study, and the dose of pimurutamab in Part II will be determined based on the results of Part I. Participants will be randomized in a 1:1 ratio to one of two groups. Experimental group: pimurutamab in combination with serplulimab and chemotherapy, administered Q3W for 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab. Control group: placebo in combination with pembrolizumab and chemotherapy, administered Q3W for 4 cycles, followed by maintenance therapy with placebo in combination with pembrolizumab. The primary endpoints of Part II are PFS assessed by BICR, and overall survival (OS). The primary objective of this study is to evaluate the efficacy of pimurutamab in combination with serplulimab and chemotherapy versus placebo in combination with serplulimab or pembrolizumab and chemotherapy as first-line treatment in patients with advanced sqNSCLC. Secondary objectives include evaluating the safety, pharmacokinetic (PK) characteristics, and immunogenicity of pimurutamab in combination with serplulimab and chemotherapy, as well as evaluating the relationship between EGFR and PD-L1 expression in tumour tissues and efficacy.
Henlius has established a comprehensive portfolio in the field of lung cancer, spanning multiple histological subtypes and treatment stages, and incorporating diverse therapeutic mechanisms including immunotherapy, targeted therapy, anti-angiogenic therapy, and antibody–drug conjugates (ADCs). The Company’s flagship product, serplulimab (trade name: Hetronifly® in Europe), is the world’s first anti-PD-1 monoclonal antibody approved for first-line treatment of small cell lung cancer (SCLC). It has been approved in more than 40 countries and regions worldwide, covering key first-line indications across lung cancer, including extensive-stage small cell lung cancer (ES-SCLC), squamous non-small cell lung cancer (sqNSCLC), and non-squamous non-small cell lung cancer (nsqNSCLC). In addition, the global Phase 3 multicentre clinical trial evaluating serplulimab for first-line treatment of limited-stage small cell lung cancer (LS-SCLC) has completed global patient enrolment. Meanwhile, HLX04 (bevacizumab biosimilar) further strengthens the company’s anti-angiogenic therapy portfolio in lung cancer, providing a high-quality and more affordable treatment option for patients with advanced, metastatic, or recurrent NSCLC. On the innovation front, Henlius is advancing a diversified pipeline with differentiated mechanisms of action. HLX43, a PD-L1-targeting ADC with broad anti-tumour potential and considered a potential best-in-class candidate, has demonstrated a compelling “high efficacy, low toxicity” profile across multiple tumour types including lung cancer, and clinical trials have been initiated in China, the United States, Japan, and Australia. In addition, the combination regimen of the anti-EGFR mAb pimurutamab with serplulimab has shown breakthrough clinical signals in EGFR-high-expressing sqNSCLC, further advancing precision treatment strategies. The Company’s early-stage pipeline also includes HLX3901, a DLL3 × DLL3 × CD3 × CD28 tetravalent T-cell engager being developed for SCLC, and HLX48, a bispecific ADC targeting EGFR × cMet for the treatment of NSCLC.
Looking ahead, Henlius will continue to deepen its innovation strategy in lung cancer, leveraging a diversified product portfolio and global clinical development capabilities to deliver more breakthrough treatment options for patients and generate greater clinical and societal value.
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