On December 2, 2022, the updated results of ASTRUM-005, Henlius’ phase 3 clinical study of anti-PD-1 mAb HANSIZHUANG (serplulimab) as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), were released in the European Society for Medical Oncology Asia (ESMO Asia) Congress. The study results were accepted as Late-breaking Abstract and were presented by Professor Ying Cheng from Jilin Cancer Hospital.
The NDA of Serplulimab for the treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA), and is expected to be the world’s first PD-1 inhibitor for the first-line treatment of SCLC. On Novemember 29, the first patient was dosed in NCT05468489, a bridging head-to-head trial conducted in the United States aming to compare serplulimab to standard of care atezolizumab (anti-PD-L1 mAb). Based on the positive feedback from FDA Biologics license Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion results of the FDA's Type C consultation meeting, Henlius plans to recruit 100 pairs of US patients with ES-SCLC to evaluate the efficacy of HANSIZHUANG.
Updated results of ASTRUM-005 is as follows:
ES-SCLC
Title: Updated results of first-line serplulimab versus placebo combined with chemotherapy in extensive-stage small-cell lung cancer: an international multicentre phase 3 study (ASTRUM-005)
Leading PI: Ying Cheng, Jilin Cancer Hospital
Abstract No.: LBA9
Session: Proffered Paper session/Thoracic cancers
Form: Oral presentation
Presentation Time: 2 December 2022, 14:40 - 14:50 UTC+8
Study design
ASTRUM-005 (NCT04063163) is a randomised, double-blind, international, multicentre, phase 3 study aimed to compare the efficacy and safety of serplulimab, a novel anti-PD-1 antibody, versus placebo in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients. Eligible patients were randomised 2:1 to receive serplulimab 4.5 mg/kg or placebo combined with carboplatin and etoposide intravenously every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate, duration of response, and safety.
Results
• Efficacy
Median OS was improved in the serplulimab group than that in the placebo group (15.8 vs. 11.1 months; hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.50–0.76; descriptive p<0.001). Median PFS assessed by the independent radiology review committee per RECIST v1.1 was also prolonged with the addition of serplulimab (5.8 vs. 4.3 months; HR 0.47, 95% CI 0.38–0.58). Subgroup analysis of OS by race showed similar trends to improved survival in Asians and non-Asians.
• Satety
Grade ≥3 treatment-related adverse events (AEs) were reported in 75.6% and 75.5% patients in the respective groups.
Conclusions
The promising efficacy and favourable safety of serplulimab plus chemotherapy for untreated ES-SCLC were maintained. Subgroup analysis revealed consistent survival benefits. ASTRUM-005 supports the development of serplulimab as the first PD-1 inhibitor combined with chemotherapy for untreated ES-SCLC.
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 11 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 forging ahead. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 11 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 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 small cell lung cancer (SCLC). Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC, and the related clinical trial has also become the first study published in JAMA on SCLC immunotherapy. Serplulimab was also granted orphan drug designation by the FDA for treatment of SCLC.