Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first interim analysis met the primary study endpoint of the overall survival (OS) of the Phase 3 clinical study (NCT04063163) of its innovative PD-1 inhibitor serplulimab in combination with chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC). There is no anti-PD-1 mAb approved for the treatment of extensive-stage small cell lung cancer (ES-SCLC) worldwide.

The study's main purpose is to explore the efficacy and safety of serplulimab in combination with chemotherapy in previously untreated patients with ES-SCLC. Based on the results of a pre-defined interim analysis conducted by the Independent Data Monitoring Committee (IDMC), serplulimab in combination with chemotherapy showed a significant improvement in OS against chemotherapy, which met the pre-defined efficacy criteria, with good safety and no detection of a new safety signal. IDMC suggested that the company can hence communicate with healthy authority.

Professor Ying Cheng, the principal investigator of NCT04063163, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, "I'm very excited to see that the Phase 3 study of serplulimab in ES-SCLC has met its primary endpoint OS, and its efficacy and safety have been fully validated. This study is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results show China's ability to innovate with a high clinical trial level. We are looking forward to serplulimab launching as soon as possible, which brings a drug with Chinese independent intellectual property to patients with small cell lung cancer all over the world."

IDMC Chairman of NCT04063163, and Cancer Hospital Chinese Academy of Medical Sciences, Professor Jie Wang, said, "SCLC is a type of lung cancer with strong invasion and poor prognosis, among which ES-SCLC cancer cells are prone to metastasis. At present, ES-SCLC is still mainly treated with chemotherapy or chemotherapy combined with PD-L1 inhibitors. It is easy to progress after chemotherapy, and the 5-year survival rate is generally less than 5%. The prognosis has not been improved for a long time. The results of the Phase 3 trial of serplulimab bring a new option for anti-PD-1 mAb as a first-line ES-SCLC therapy."

Professor Giorgio Scagliotti from the Medical Oncology, University of Turin in Italy, one of IDMC members, said, "There are limited choices for SCLC clinical treatment, especially in anti-PD-1 mAb. Currently, the first-line treatment is chemotherapy or anti-PD-L1 mAb combined with chemotherapy according to the NCCN guidelines. This international multi-center Phase 3 clinical study on ES-SCLC has been carried out in many countries in Asia and Europe, witmore than 580 subjects worldwide. It is believed that by means of international multi-center clinical data, serplulimab will enter the international market and benefit more patients worldwide."

Mr. Jason Zhu, President of Henlius, said, "Serplulimab is an innovative mAb independently developed by Henlius, and the company has carried out a comprehensive first-line treatment layout for lung cancer. Based on the large number of unmet clinical needs, the company has invested in SCLC. The excellent results of this Phase 3 study are expected to contribute serplulimab in becoming the first anti-PD-1 mAb for the first-line treatment of SCLC, which will significantly improve the overall prognosis. Henlius focuses on high-incidence cancers both globally and in China. In the future, we will proactively promote the combination immunotherapy of serplulimab and international clinical research, benefiting more patients around the world."

SCLC is highly malignant, and the available treatment is limited

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. 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. SCLC accounts for 15%-20% among LC, and is the most aggressive subtype of LC, which is divided into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are already in extensive stage when diagnosed. Patients with ES-SCLC always have rapid tumour growth and poor prognosis. Some of them have shorter survival due to extensive tumor metastasis and poor physical status only with supportive care.

Over 20 years, etoposide plus carboplatin/cisplatin is still the standard of care for ES-SCLC, but 80% of patients with limited stage disease and almost all patients with extensive stage disease relapse within one year, with a median survival of only 4 to 5 months after relapse. The emergence of immune checkpoint inhibitors provides a new option. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. However, the application of immunotherapy in ES-SCLC still faces challenges. In recent years, a number of PD-1 mAbs have failed in the area. Therefore, more effective first-line treatment of PD-1 inhibitors is urgently needed.

Centering on the unmet needs of patients, covering the first-line treatment of all types of lung cancer

Henlius has adopted a differentiated "Combo+Global" strategy on serplulimab. Currently, serplulimab has been approved for clinical trials in China, the United States, the European Union and other countries and regions. A total of 10 immuo-oncology therapies clinical trials of serplulimab are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover LC, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma  and gastric cancer etc. Up to date, about 2300 patients have been enrolled worldwide, proving that the quality of serplulimab has built trust in foreign markets. In April, the New Drug Application (NDA) of serplulimab for the treatment of MSI-H solid tumours was accepted by the National Medical Products Administration (NMPA) and granted priority review, which is expected to be approved in the first half of 2022.

According to the characteristics of cancer patients both globally and in China, the company focus on lung cancer and gastrointestinal cancer with serplulimab as the backbone. 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 SCLC, covering more than 90% of lung cancer patients. Based on a randomized, double-blind, international multi-center Phase 3 clinical trials conducted in previously untreated patients with locally advanced or metastatic sqNSCLC, the NDA of serplulimab for first-line treatment of locally advanced or metastatic sqNSCLC has been accepted by the NMPA. In the future, with abundant international clinical research data, Henlius will continue expanding the international distribution of serplulimab and benefit more patients around the world.

Source: Henlius