全球研发 | 复星医药子公司复宏汉霖抗EGFR单抗HLX07联合方案II 期研究更新数据于WCLC 2025发布

在全球非小细胞肺癌（NSCLC）患者中，EGFR高表达的比例约为40%–89%（取决于病理分型、种族等因素），意味着每年有数百万新发患者属于这一人群^[1-3]。尤其是在sqNSCLC患者中，EGFR高表达患者占比达89%^[1-2]。

然而，与携带EGFR驱动突变患者相比，EGFR高表达人群通常缺乏适用于EGFR靶向治疗的驱动突变，因此目前无法实现精准治疗。另一方面，尽管PD-(L)1抑制剂已被纳入晚期或转移性sqNSCLC一线治疗的主流方案，但针对EGFR高表达人群，迄今尚无经验证的一线治疗方案。这一庞大人群仍面临治疗匮乏、生存率低、预后差等多重困境，亟需创新方案填补这一临床空白。

HLX07是复宏汉霖自主开发的创新EGFR的单克隆抗体。相比西妥昔单抗该产品具备更低的免疫原性和更好的靶点亲和力。同时通过Fc端改造，HLX07大大延长了产品的半衰期，3周的给药频率使其更适合与肿瘤免疫产品的临床联用。临床前研究表明，HLX07具有更出色的生物活性，在不同肿瘤模型中均能显著抑制肿瘤细胞的生长，并与H药显示出很强的协同作用^[4]。H药作为全球首个一线获批用于广泛期小细胞肺癌的抗PD-1单抗，迄今已惠及逾12万名患者，覆盖全球近半数人口。两者联用，不仅阻断EGFR生长信号，更同步激活免疫应答，极具联合协同治疗潜力。

A组和B组中，独立影像评估委员会（IRRC）根据RECIST 1.1评估的确认ORR分别为69.2%（95% 置信区间[CI] 38.6–90.9）和71.4%（95% CI 41.9–91.6），疾病控制率分别为92.3%（95% CI 64.0–99.8）和100%（95% CI 76.8–100.0）。

截至数据截止日期，两组的中位总生存期和持续缓解时间均未达到。

A New First-Line Option for EGFR Overexpression Patients: Henlius Presents Updated Phase 2 Data of HLX07 Combination Therapy in sqNSCLC

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.