Recently, the first subject was dosed in a Phase 2 clinical trial (NCT04976647) of serplulimab, a novel anti-PD-1 monoclonal antibody (mAb) developed by Henlius, in combination with HLX07, a novel anti-EGFR mAb, for the first-line treatment of EGFR high expression squamous non-small cell lung cancer (sqNSCLC). Currently, anti-PD-1 mAbs are commonly used in combination with chemotherapy for no oncology driver sqNSCLC patients. The company screened high EGFR expression patients and carried out Phase 2 clinical trial of serplulimab in combination with HLX07 in these patients, with the aim of reshaping the standard of care for the first-line in this field.
According to GLOBOCAN data, lung cancer (LC) is the second commonly diagnosed cancer globally and accounts for 11.4% of the global cancer incidence in 2020[1]. It is estimated that there are 810,000 new cases with LC in China in 2020, and LC is the leading cause of cancer incidence and mortality[2]. NSCLC accounts for about 85% among LC, with sqNSCLC accounting for about 40%[3]. EGFR is known to be expressed more abundantly in malignant than in normal tissue, including 40%–80% of NSCLC[4]. Among NSCLC 30-40% is high expression[5]. In recent years, immuno-oncology therapy has made great progress in LC, and PD-1 inhibitors are one of the main treatments for advanced or metastatic sqNSCLC. However, there is no treatment recommended for EGFR high expression sqNSCLC patients in guidelines. It is expected that PD-1 target combined with EGFR target treatment would provide innovative treatment with better efficacy for these patients.
Serplulimab is Henlius’ self-developed innovative mAb. With the differentiated "Combo+Global" strategy on serplulimab, serplulimab has been approved for clinical trials in China, the United States, the European Union and other countries and regions. A total of 11 immuo-oncology therapies clinical trials of serplulimab are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover lung cancer, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer etc. In April, the New Drug Application (NDA) of serplulimab for the treatment of MSI-H solid tumours was accepted by the NMPA and granted priority review. It is expected to be approved in the first half of 2022. Henlius has achieved a comprehensive first-line clinical layout of LC, and has carried out trials on serplulimab in sqNSCLC, non-squamous non-small cell lung cancer and small cell lung cancer, covering more than 90% of LC patients. The NDA of serplulimab combined with chemotherapy in locally advanced or metastatic squamous non-small cell lung cancer was accepted by NMPA in September 2021. The international multi-center Phase 3 study of serplulimab in combination with chemotherapy in previously untreated extensive small-cell lung cancer recently reached the primary endpoint. Henlius will proceed to file the regulatory applications for this indication as soon as possible. It is expected to be the first anti-PD-1 mAb for first-line treatment of SCLC.
HLX07, a humanised anti-EGFR mAb, is a bio-better independently developed by Henlius. Adopting the self-developed advanced antibody engineering platform, Henlius re-engineered cetuximab by humanizing its Fab regions and minimizing its glycan contents to generate HLX07 to reduce the immunogenicity and increase its affinity. Pre-clinical studies have shown that HLX07 binds to EGFR with similar affinity and favorable safety profile and has better bioactivity compared to cetuximab. HLX07 can significantly inhibit the growth in different tumour models and synergize with immune checkpoint inhibitors such as serplulimab[6]. The company is proposing to commence more Phase 2 clinical trial of serplulimab combined with HLX07 on other tumours in the near future.
Looking forward, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.
About NCT04876647
This two-part phase 2 study aims to compare the efficacy and safety of HLX07 plus serplulimab and chemotherapy (carboplatin-nab-paclitaxel) versus serplulimab plus chemotherapy versus HLX07 plus serplulimab in previously untreated patients with locally advanced, recurrent, or metastatic squamous non-small cell lung cancer (sqNSCLC). Part 1 is a single-arm safety run-in portion, in which eligible patients will receive HLX07 plus serplulimab and chemotherapy. Part 2 is a randomised, open-label, multicentre phase 2 study. Eligible patients will be randomised 1:1:1 to receive intravenous infusion of HLX07 plus serplulimab and chemotherapy, serplulimab plus chemotherapy, or HLX07 plus serplulimab every three weeks. The primary objective of this study is to compare the clinical efficacy of the three treatments as first-line therapies for locally advanced/recurrent or metastatic high EGFR expression (H score≥200) sqNSCLC patients. The primary endpoints are objective response rate (ORR) and progression-free survival (PFS) assessed by independent radiological review committee (IRRC) per RECIST v1.1. Secondary objectives include the evaluation of other efficacy endpoints, safety, tolerability, immunogenicity, and pharmacokinetic profiles.
Reference
[1] Sung H,Ferlay J,Siegel RL,Laversanne M,SoerjomataramI,Jemal A,Bray F.Global cancer statistics 2020:GLOBOCAN estimates of incidenceand mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin.2021Feb 4.
[2] Cao W, Chen HD, Yu YW, Li N, Chen WQ.Changing profiles of cancer burden worldwide and in China: a secondary analysisof the global cancer statistics 2020. Chin Med J (Engl). 2021;134(7):783-791.
[3]Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. CancerEpidemiol Biomarkers Prev. 2019 Oct;28(10):1563-1579. doi:10.1158/1055-9965.EPI-19-0221.
[4] Ettinger D S. Clinical implications of EGFR expression in thedevelopment and progression of solid tumors: focus on non‐small cell lungcancer[J]. The oncologist, 2006, 11(4): 358-373.Pei-Hua Lin, Chi-Ling.
[5] Pirker R, Pereira J R, Von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study[J]. The lancet oncology, 2012, 13(1): 33-42.
[6] Tseng,Yun-Chih Cheng, Chieh-Hsin Ho, Shih Chieh Chen, Yanling Wang, Eugene Liu,Hassan Issafras & Weidong Jiang (2021) Distinguishing features of a novelhumanized anti-EGFR monoclonal antibody based on cetuximab with superiorantitumor efficacy, Expert Opinion on Biological Therapy, 21:11, 1491-1507.