Shanghai, China, May 15, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient 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). The leading principal investigator is Professor Rui-Hua Xu from Sun Yat-sen University Cancer Center and State Key Laboratory of Oncology in South China.
Currently, for mCRC patients, immunotherapies have been proven to bring hope to patients with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) but have not yet shown meaningful positive outcomes in those with proficient mismatch repair (pMMR)/ microsatellite stable (MSS), and there is no immunotherapy approved globally for the first-line treatment of mCRC. HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for the first-line treatment of mCRC.
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 2020, and the incidence rates were highest in Europe and Australia and New Zealand [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 [1]. 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].
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 [6,7]. The standard of care for mCRC involves the combination of vascular endothelial growth factor (VEGF) inhibitor, such as bevacizumab, and systemic chemotherapy [3-5]. However, 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. Therefore, the benefit of adding immunotherapy to standard-of-care for this group of patients remains unclear. Previously, HANSIZHUANG was approved in China for the treatment of MSI-H solid tumours in March 2022, with its excelent efficacy data, and then was recommended by the CSCO Guidelines for Colorectal Cancer and the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor.
The company is continuing to explore immuno-oncology therapy for mCRC, with the goal of delivering more effective treatment for a broader population of patients. The results of ASTRUM-015 were first presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). As of January 20, 2022, 114 patients were enrolled in ASTRUM-015 study, among which 90 out of the 94 (95.7%) with available MSI status were MSS. The results demonstrated that serplulimab plus bevacizumab and chemotherapy (XELOX) improved PFS and other efficacy endpoints compared to placebo plus bevacizumab and XELOX, with a manageable safety profile. Additionally, the updated results of ASTRUM-015 will be released online and presented in poster sessions at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
In the future, Henlius will continue to emphasise unmet clinical needs with a patient-centric approach and actively promote the development of ASTRUM-015 to benefit more patients around the world with high-quality, affordable and innovative biologics.
【Reference】
[1] WHO Colorectal Cancer Fact Sheets, Available from: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer, accessed [15 May 2024]
[2] B Han et al. J Natl Cancer Cent, 4(1), 47-53 (2024)
[3] Iwasa, S. et al. Cancer Commun (Lond) 43, 519-522 (2023).
[4] Hurwitz, H. et al. N Engl J Med 350, 2335-2342 (2004).
[5] Benson, A. B. et al. J Natl Compr Canc Netw 20, 1139-1167 (2022)
[6] Diaz, L. A., Jr. et al. Lancet Oncol 23, 659-670 (2022).
[7] Lenz, H. J. et al. J Clin Oncol 40, 161-170 (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 ASTRUM-015
This randomised, double-blind, multicentre, three-stage phase 2/3 study aims to evaluate serplulimab (anti-PD-1 antibody) plus bevacizumab and chemotherapy (XELOX) versus placebo plus bevacizumab and chemotherapy (XELOX), as first-line treatment for metastatic colorectal cancer (mCRC). Stage 1 is a single-arm safety run-in stage; its primary endpoints are safety and tolerability in Cycle 1. Stage 2 is a multicentre, randomised, double-blind, parallel-controlled phase 2 study, whose primary endpoint is progression-free survival as assessed by independent radiological review committee per RECIST v1.1. Secondary endpoints include other efficacy measures, safety, pharmacokinetics, and quality-of-life. Stage 3 is a phase 3 study conducted based on the results of the phase 2 study. Eligible patients are randomly assigned (1:1) to receive intravenous serplulimab 300 mg + bevacizumab 7.5 mg/kg + XELOX (group A) or placebo + bevacizumab 7.5 mg/kg + XELOX (group B), every three weeks. The primary and secondary endpoints of the phase 3 study are the same as those of the phase 2 study.