Henlius' anti-PD-1 mAb MRCT achieved 15.38 months OS in first-line treatment of SCLC, reducing the risk of death by 38% of the overall population

The ASTRUM-005 states that serplulimab combined with carboplatin-etoposide prolonged median OS in both the overall population and the Asian subgroup,the median overall survival (OS) in the serplulimab and placebo groups were 15.38 and 11.10 months,respectively,reducing risk of death by 38% (41% in the Asian subgroup),p <0.001. The 2-year OS rate (OSR) in the two treatment groups were 43.2% and 8.0%,respectively. Serplulimab also has a manageable safety profile.

It is expected that serplulimab will become the first anti-PD-1 mAb in first-line small cell lung cancer treatment,providing a new treatment option for patients. There is no anti-PD-1 mAb approved for the treatment of extensive-stage small cell lung cancer worldwide.

Keytruda and Opdivo,anti-PD-1 monoclonal antibody products,failed in the first-line of SCLC clinical trial. Their NDAs for relevant indications were withdrawn.

SHANGHAI,Dec. 20,2021 --Shanghai Henlius Biotech,Inc. (2696.HK) successfully held its Global R&D Day themed "H-evolution: From Biotech to Biopharma",and released its interim analysis results of Phase 3 clinical study (ASTRUM-005) in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC) of serplulimab (novel anti-PD-1 mAb).

The study states that serplulimab combined with carboplatin-etoposide prolonged median overall survival (OS)in both the overall population and the Asian subgroup,the median OS in the serplulimab and placebo groups were 15.38 and 11.10 months,respectively. Serplulimab also has a manageable safety profile. It is expected that serplulimab will become the first anti-PD-1 mAb in first-line SCLC treatment,providing a new treatment option for patients.

An urgent need for new drugs to break the enduring plight

According to GLOBOCAN 2020,lung cancer (LC) is the second commonly diagnosed and the first mortality cancer around the world,and the leading cause of cancer incidence and mortality in China. It is estimated that there are more than 810,000 new cases reported in 2020,accounting for 17.9% of new cancer cases in China,in which SCLC is the most malignant subtype of LC with 15%-20% among LC. The SCLC breaks down into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are in extensive stage when diagnosed. Their clinical condition deteriorates rapidly and the overall prognosis is poor. In the past 20 years,etoposide combined carboplatin/cisplatin was still the standards of care for ES-SCLC,but almost all patients with extensive stage relapse within one year,with a median OS of only 10 to 11 months. The advent of immune checkpoint inhibitors brings hope to patients. 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. Data showed that the median OS was about 12-13 months in the anti-PD-L1 mAb groups and about 10 months in the chemotherapy groups. 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.

Significantly improved patients' OS,serplulimab vs. placebo groups: OS 15.38 months vs. 11.10 months,2-year OSR 43.2% vs. 8.0%

ASTRUM-005 is the international multi-cetner clinical research and its principal investigator is Professor Ying Cheng,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. This study has set up about 128 sites in China,Poland,Russia,Turkey,Ukraine and Georgia,etc. 585 subjects were enrolled,among whom 31.5% were Caucasian. The enrolled patients are randomised 2:1 to receive intravenous infusion of either serplulimab or placebo in combination with chemotherapy every-3-week,until disease progression,death,intolerable toxicity,withdrawal of informed consent or other reasons specified in the protocol (whichever occurs first). The primary objective of this study is to compare the clinical efficacy of the two treatments as first-line therapies for ES-SCLC patients,and the secondary objectives are to evaluate the safety and tolerability. The primary endpoint is OS,and secondary endpoints include progression-free survival (PFS),PFS2,objective response rate (ORR),duration of response (DOR),safety,pharmacokinetic characteristic,and immunogenicity,etc.

By the cut-off date (Oct 22,2021),585 eligible subjects were enrolled in this study (serplulimab group: n=389; placebo group: n=196),with a median follow-up duration of 12.3 months. The median OS in the serplulimab and placebo groups were 15.38 and 11.10 months,with a hazard ratio (HR) of 0.62 (95% CI: 0.48,0.80),respectively. In Asian subgroup,the median OS in the serplulimab and placebo groups were 16.03 and 11.10 months,with a hazard ratio (HR) of 0.59 (95% CI: 0.44,0.79),p <0.001. The results demonstrated that as first-line therapy,serplulimab in combination with carboplatin-etoposide significantly improved the OS in ES-SCLC patients with a manageable safety profile. On December 7,an interim analysis was conducted by the Independent Data Monitoring Committee (IDMC) for this study. IDMC suggested that the company can hence communicate with healthy authority.

Based on the promising data of this study,Henlius will proceed to file the regulatory applications for this indication as soon as possible. In the future,the company will continue putting the unmet clinical needs as the first priority,proactively promoting the combination immunotherapy of serplulimab and international regulatory registration,to benefit more patients around the world.

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