Shanghai, China, January 5, 2023-Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in an international multi-centre phase 3 clinical trial (NCT05353257) of the company’s self-developed anti-PD-1 mAb HANSIZHUANG (serplulimab) in combination with chemotherapy and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC) in the United States. The co-leading principal investigators are Jinming Yu, an Academician of the Chinese Academy of Engineering (CAE) and the Director of Shandong Cancer Hospital, Ligang Xing, the vice Director of Shandong Cancer Hospital, and Ying Cheng, the Director of Jilin Cancer Hospital. Previously, the first patient was dosed in China, and the clinical trial applications of NCT05353257 have been approved including in the EU and Australia.
According to GLOBOCAN 2020, lung cancer (LC) is the second most commonly diagnosed and the first mortality cancer around the world. There were 2.2 million new LC cases and 1.8 million new deaths in 2020 worldwide, and LC is still the leading cause of cancer deaths[1]. Small cell lung cancer (SCLC) accounts for 15%–20% of the total number of LC, which is featured by high malignancy, strong invasiveness, early metastasis, and rapid disease progression, with extremely poor prognosis. LC is divided into two stages, including limited stage and extensive stage, and 30%–40% patients are in limited stage at the time of diagnosis. The standard treatment regimens for LS-SCLC are surgery, chemotherapy and concurrent radiotherapy. Traditional chemotherapeutic drugs did not exhibit significant progress in patients with LS-SCLC, and most patients tend to develop drug resistance or rapid relapse[2–4]. The advent of immune checkpoint inhibitors has been proven to bring hope to patients with ES-SCLC but has not yet shown benefit in those with LS-SCLC. Recently, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer for the treatment of ES-SCLC. The company is continuing to explore immuno-oncology therapy for LS-SCLC, with the goal of delivering more effective treatment for patients.
HANSIZHUANG is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of MSI-H solid tumours and non-small cell lung cancer. Regarding unmet clinical needs as a core, Henlius covers the full range of first-line treatments of LC. Two global multi-centre phase 3 clinical trials regarding squamous non-small cell lung cancer (sqNSCLC) and ES-SCLC have been conducted in China, Turkey, Poland, Georgia, and other countries and regions, with over 30% of the total enrolled subjects being White, providing more diverse cases for clinical research. ASTRUM-005, the international multi-centre, phase 3 study in patients with ES-SCLC, has been published in The Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world, making ASTRUM-005 became the first study published in JAMA on SCLC immunotherapy. Based on the results, the NDA is under review of HANSIZHUANG for the first-line treatment of ES-SCLC by the NMPA, and it is expected to become the world's first anti-PD-1 mAb for the first-line treatment of SCLC and to fill the clinical gap in the next five years. Moreover, HANSIZHUANG has been granted orphan-drug designations for the treatment of SCLC by the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively. It is worth mentioning that the first patient has been dosed in a bridging head-to-head trial in the US to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, which is expected to propel the product towards US market approval further.
In the future, the company will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of serplulimab and international commercialization process to benefit more patients around the world.
About NCT05353257
This randomised, double-blind, international multi-centre, phase 3 clinical study aims to compare the efficacy and safety of serplulimab versus placebo, in combination with chemotherapy (carboplatin/cisplatin-etoposide) and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC). Eligible patients will be randomised at a ratio of 1:1. The primary objective of this study is to evaluate the anti-tumour activity of serplulimab plus chemotherapy and concurrent radiotherapy in LS-SCLC patients. The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) assessed by investigators per RECIST 1.1, as well as safety and immunogenicity.
About HANSIZHUANG
HANSIZHUANG (recombinant humanised anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 2 indications are approved for marketing in China, 2 NDAs have been accepted by the NMPA, and more than 10 clinical trials are ongoing across the world.
HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours and squamous non-small cell lung cancer (sqNSCLC). Its synergy with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 12 clinical trials on immuno-oncology combination therapies in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was respectively recommended for the first-line treatment of ES-SCLC in the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) and the treatment of esophageal cancer (category IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer. The associated clinical trial became the first study published in JAMA on SCLC immunotherapy. Serplulimab was also granted orphan drug designations by the FDA and EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC.
【参考文献】
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