Recently, the phase 2 study of HANSIZHUANG (serplulimab) in patients with microsatellite instability-high (MSI-H) solid tumours was published in the prestigious journal British Journal of Cancer (IF 9.075). Serplulimab demonstrated a durable anti-tumour effect and a manageable safety profile in patients with previously treated MSI-H solid tumours. Based on the trial results, HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours.
The deficiency in mismatch repair (MMR) can lead to mismatched bases and insertion/deletion mutations in microsatellites during DNA replication, and the accumulation of mutations usually causes MSI[1]. The burden of MSI-H cancers is estimated to be more than 1 million and about 0.3 million new cases per year worldwide and in China, respectively[2–6]. MSI-H is commonly found in endometrial cancer, colorectal cancer, and gastric cancer, among others. These patients usually have high response to immune checkpoint inhibitors[7-8]. Anti-PD-1/PD-L1 mAbs have good therapeutic effect for patients with MSI-H solid tumours.
This single-arm, open-label, multicentre, phase 2 study aimed to evaluate the efficacy, safety, and tolerability of serplulimab in patients with unresectable or metastatic MSI-H/dMMR solid tumours who had progressed on or were intolerant to standard therapies. Patients with previously treated unresectable or metastatic MSI-H/dMMR solid tumours received intravenous serplulimab 3 mg/kg every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumours v1.1. Secondary efficacy endpoints included ORR assessed by investigators, progression-free survival (PFS), overall survival (OS), and duration of response (DoR). As of 9 January 2021, 108 patients were enrolled, and 68 patients with MSI-H solid tumours confirmed at the central laboratory or local study sites were included in the main efficacy analysis population (MEAP). The median follow-up duration in the MEAP was 7.7 months, with an IRRC-assessed ORR of 38.2% (95% confidence interval [CI]: 26.7, 50.8). In MEAP, median PFS, OS, and DoR were not reached (NR). The 12-month PFS rate assessed by IRRC was 61.9% (95% CI: 49.0, 72.5); 12-month OS rate was 81.2% (95% CI: 67.8, 89.4); and 12-month DoR rate assessed by IRRC was 95.7% (95% CI: 72.9, 99.4). Serplulimab demonstrated a durable anti-tumour effect and a manageable safety profile in previously treated patients with MSI-H solid tumours, suggesting that it is a promising tissue-agnostic treatment.
In the future, Henlius will continue to conduct clinical studies on more innovative products, with antibody technology as the core, and proactively explore immuno-oncology combination therapy, bispecific antibodies, and antibody-drug conjugates (ADC), with the aim of bringing affordable and high-quality innovative biologics to patients around the world.
About British Journal of Cancer
The British Journal of Cancer (BJC) is one of the most cited general cancer journals, committed to publishing cutting edge discovery, translational and clinical cancer research. The BJC aims to provide a global platform to disseminate important research within the broad spectrum of oncology. The journal welcomes research across all cancer types and has a focus on: metastasis, microenvironment, immunology and immunotherapy, targeted and next-generation therapeutics, chemotherapy and radiotherapy, mechanisms of resistance, clinical trials, genomics, epigenomics and precision medicine, epidemiology, metabolism and state-of-the art diagnostic approaches.
Reference
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