Shanghai, China, October 24, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient in Japan has been dosed in the phase 3 stage of the international multi-centre clinical trial (ASTRUM-015) of the company’s self-developed anti-PD-1 mAb HANSIZHUANG (serplulimab) in combination with bevacizumab and chemotherapy in patients with metastatic colorectal cancer (mCRC). Previously, the ASTRUM-015 study had launched its phase 3 stage and completed the first patient dosing in China and Indonesia.
Colorectal cancer (CRC) is one of the most common malignant cancers globally. Over 1.9 million newly diagnosed cases and more than 900,000 deaths were estimated in 2022 [1]. It is estimated that, by 2040, the burden of CRC will increase to 3.2 million new cases per year (an increase of 63%) and 1.6 million deaths per year [2]. According to the latest report by National Cancer Center (NCC) of China, the incidence and mortality of CRC in China ranked 2nd and 4th among all cancers with 517,000 new cases and 240,000 deaths in 2022 [2]. In Japan, CRC ranks first in new incidence and second in mortality among all malignant tumors, with 146,000 new cases and 60,000 deaths reported in 2022 [1].
CRC often spreads before the initial tumour is detected. Based on molecular phenotype, mCRC is generally divided into two groups, dMMR/MSI-H and pMMR/MSS, with the latter accounting for around 95% of mCRC [3,4]. The standard of care for mCRC involves the combination of vascular endothelial growth factor (VEGF) inhibitor, such as bevacizumab, and systemic chemotherapy [5-7]. Still, sustained efficacy and prognosis remain to be improved. Several PD-1 inhibitors were shown to confer significant survival benefits for advanced CRC patients with dMMR/MSI-H [8,9]. However, pMMR/MSS mCRC, which accounts for a much higher proportion of mCRC, are considered “immune-cold tumours” characterised by low response rate to immunotherapy. To date, there has been no globally approved immunotherapy for the first-line treatment of pMMR/MSS mCRC, indicating a significant unmet medical need for this patient population.
The company is continuing to explore immuno-oncology therapy for mCRC, with the goal of delivering highly effective treatment for a broad population of patients. ASTRUM-015 trial is a phase 2/3 study of HANSIZHUANG (serplulimab) plus bevacizumab and chemotherapy as first-line treatment for patients with mCRC. The results of the phase 2 stage of ASTRUM-015 were presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) and 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Recently, the results were also published online in Med, demonstrating the global recognition of serplulimab by the community. In conclusion, the addition of serplulimab to bevacizumab and chemotherapy conferred a numerically longer median progression-free survival, along with a manageable safety profile for mCRC patients as a whole, and those with MSS mCRC. These results support serplulimab plus bevacizumab and chemotherapy as a promising first-line treatment option for mCRC that warrants further investigation.
Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG (serplulimab) with in-house products of the company and innovative therapies are being actively promoted. The company has initiated over 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,400 subjects enrolled. Moving forward, Henlius will actively promote the clinical progress of the phase 3 stage of ASTRUM-015. With the accelerated progress, HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for previously untreated mCRC and fill the clinical gap in first-line immunotherapy in these patients.
【Reference】
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
[2] WHO Colorectal Cancer Fact Sheets, Available from: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer, accessed [15 May 2024]
[3] Diaz, L. A., Jr. et al. Lancet Oncol 23, 659-670 (2022).
[4] Lenz, H. J. et al. J Clin Oncol 40, 161-170 (2022).
[5] Iwasa, S. et al. Cancer Commun (Lond) 43, 519-522 (2023).
[6] Hurwitz, H. et al. N Engl J Med 350, 2335-2342 (2004).
[7] Benson, A. B. et al. J Natl Compr Canc Netw 20, 1139-1167 (2022)
[8] Overman MJ, Kopetz S, McDermott RS, et al. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results (abstract). J Clin Oncol 34, 2016 (suppl; abstr 3501).
[9] Overman MJ, Lonardi S, Wong KYM, et al. Durable Clinical Benefit with Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 2018; 36:773.
About HANSIZHUANG
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC and has been approved in China and several SEA countries. Up to date, 4 indications are approved for marketing, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world.
HANSIZHUANG was approved in China in March 2022 and has been approved by the National Medicinal Products Administration (NMPA) for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). The marketing applications of the first-line treatment for non-squamous non-small cell lung cancer (nsNSCLC) and ES-SCLC are under review by the NMPA and the European Medicines Agency (EMA), respectively. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. The company has initiated more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,000 subjects enrolled in China, the U.S., Turkey, Poland, Georgia and other countries and regions. The results of 4 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine, Cancer Cell and British Journal of Cancer, respectively. Furthermore, HANSIZHUANG was respectively recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.