ASTRUM-005: The first immunotherapy clinical study of SCLC published in JAMA, one of the top medical journals in the world

• ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC.
• In ASTRUM-005, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC. Compared with chemotherapy, the treatment prolonged median OS by 4.5 months and had the lowest HR of 0.63.
• HANSIZHUANG (serplulimab) 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.

SHANGHAI, Sept. 28, 2022 /PRNewswire/ -- Shanghai Henlius Biotech, Inc. (2696.HK) announced that ASTRUM-005, an international multi-centre study led by Professor Ying Cheng, 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. ASTRUM-005 trial is a phase 3 study of HANSIZHUANG (serplulimab), an anti-PD-1 monoclonal antibody (mAb) developed by Henlius independently, plus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). After Prof. Ying Cheng orally presented them at the 2022 ASCO annual meeting, the results of ASTRUM-005 attract wide attention among the global research community. And now, ASTRUM-005 makes its way to the international arena once again, demonstrating the high level of academic acclaim on a global scale, the intelligence of Chinese researchers, and the strength of Chinese pharmaceuticals in terms of independent innovation research and clinical development.

Prof. Ying Cheng, the corresponding author and first author, as well as the leading principal investigator of the study, from Jilin Cancer Hospital, said, "In the ASTRUM-005 trial, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC. Compared with chemotherapy, the treatment prolonged median OS by 4.5 months and had the lowest HR of 0.63. In addition, the study showed good safety and consistent efficacy over time. ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC. It is also the first international multi-centre phase 3 clinical study led by Chinese researchers to employ immunotherapy for ES-SCLC treatment, showcasing the expertise and excellence of Chinese researchers. I would like to thank all patients and their families, as well as researchers who contributed to this study. It opens a new chapter in first-line ES-SCLC immunotherapy, which will benefit a large number of patients."

OS 15.4 months, a new record

SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases. Both limited stage SCLC (LS-SCLC) and ES-SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC. At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines at home and abroad as the first-line treatment for ES-SCLC. Compared with chemotherapy, the overall survival (OS) of patients with SCLC has been prolonged to a certain extent, but the improvements were still modest, suggesting the need for more effective treatments in this patient population.

ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy in previously untreated patients with ES-SCLC. ASTRUM-005 has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.5% were White. As of data cutoff for this interim analysis (October 22, 2021), 585 eligible patients were randomised (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. Median OS was significantly longer in the serplulimab group (15.4 months, 95% confidence interval [CI] 13.3-not evaluable) than in the placebo group (10.9 months, 95% CI 10.0-14.3) (hazard ratio [HR] 0.63, 95% CI 0.49-0.82; P <0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median progression-free survival assessed by an independent radiology review committee per RECIST v1.1 was also longer in the serplulimab group compared to the placebo group (5.7 months vs. 4.3 months; HR 0.48, 95% CI 0.38-0.59). Incidence of immune-related adverse events (irAEs) was similar to the approved PD-1/PD-L1 antibodies.

Providing more treatment options for patients worldwide

The success of ASTRUM-005 is a breakthrough in the treatment of ES-SCLC with PD-1 inhibitors. Based on the results of ASTRUM-005, the New Drug Application (NDA) of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA). Furthermore, HANSIZHUANG has been recommended for the first-line treatment of ES-SCLC by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC.

In April 2022, the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of SCLC. Based on the positive feedback from FDA Biologics License Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion on the FDA's Type C consultation meeting, Henlius is planning to soon carry out a bridging study in the US and expected to submit BLA to FDA before Q1 of 2024. At present, there is no anti-PD-1 mAb approved for the first-line treatment of SCLC worldwide. HANSIZHUANG 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.

Looking forward, Henlius will actively improving efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.

SOURCE Henlius