Apr 10, 2024｜2024
Results of Exploratory Biomarker Analysis of Pivotal Clinical Trial ASTRUM-005 of Serplulimab Initially Released at AACR 2024
Shanghai, China, April 10th, 2024 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that the exploratory biomarker analysis of ASTRUM-005, Henlius’ phase 3 clinical study of its innovative anti-PD-1 monoclonal antibody(mAb) HANSIZHUANG (serplulimab) as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) was published as poster presentation at the American Association for Cancer Research 2024 meeting (AACR 2024), with Professor Ying Cheng from Jilin Province Cancer Hospital as the leading principal investigator of this study.
HANSIZHUANG (serplulimab) is the company’s first innovative product, as well as the world's first anti-PD-1 mAb for the first-line treatment of SCLC. As of now, HANSIZHUANG has been approved in China and Indonesia, making it also the first China anti-PD-1 mAb approved in Southeast Asia. Since its first approved in China in March 2022, HANSIZHUANG has been approved for 4 indications in China including MSI-H solid tumour, squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, and esophageal squamous cell carcinoma (ESCC), benefiting more than 60,000 patients. 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. Furthermore, the company submitted marketing applications for HANSIZHUANG in Thailand, Singapore, Malaysia to further promote the product in Southeast Asia. Moreover, Henlius also launched a head-to-head bridging trial of HANSIZHUANG versus first-line standard-of-care atezolizumab for ES-SCLC in the U.S. and the company plans to submit a Biologics License Application (BLA) for HANSIZHUANG in the U.S. in 2024.
The approval of HANSIZHUANG for the treatment of ES-SCLC was primarily based on ASTRUM-005 (NCT04063163), a randomised, double-blind, international, multicentre, phase 3 study aimed to compare the efficacy and safety of serplulimab, versus placebo in combination with chemotherapy in previously untreated ES-SCLC patients. The results of ASTRUM-005 were first presented at 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and published in the Journal of the American Medical Association (JAMA), one of the top four medical journals in the world in September 2022. Thereafter, the updated results of ASTRUM-005 were released at the 2022 European Society for Medical Oncology Asia (ESMO Asia) Congress. The results of ASTRUM-005 has showed that a PD-L1 tumor proportion score (TPS)≥ 1% did not appear to be associated with better response to serplulimab plus chemotherapy. To elaborate biological characteristics of the ES-SCLC patients who has benefited from serplulimab in this study, Henlius completed an exploratory biomarker analysis to retrospectively evaluate the association of proteome signature, genetic mutations, and hematological indices with the efficacy of serplulimab.
Details of the results presented at 2024 AACR Annual Meeting are as follows:
Title
Exploratory biomarker analysis of phase 3 ASTRUM-005 study: Serplulimab versus placebo plus chemotherapy for extensive-stage small cell lung cancer
Methods
Biomarker Analysis of the ASTRUM-005 Study
Study design of ASTRUM-005 is presented in Figure 1.
Correlation analysis between the proteomic, genomic and hematological parameters of the patients and the treatment efficacy were conducted in this study. Proteomic and genomic assays were performed in the central laboratory. Serum samples were collected from patients and serum proteomics data were generated via the Olink® Explore 3072 platform. While tumour DNA was extracted from tumour samples and genomic mutations were assessed by a Med1CDxTM panel. Hematology tests were performed at hospital sites, with hematologic parameters of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels were included in the analysis.
Statistical Analysis
For the analysis of objective response rate (ORR), 95% confidence interval (CI) of rate was calculated by the Clopper-Pearson method, and the odds ratio and its 95% CI were estimated by Cochran-Mantel-Haenszel statistics. And for progression-free survival (PFS) and OS, the median was calculated from product-limit (Kaplan-Meier) estimates, while n was the number of patients in each subgroup category. The hazard ratio and its 95% CI were estimated using an unstratified Cox proportional hazards model. Efron's method was used to handle ties.
For serum proteomics, differentially expressed proteins (DEP) were identified using a t-test between responders (patients showing complete response or partial response) and non-responders (patients with stable disease or progressive disease) in the treatment group. Predictive/prognostic biomarkers are identified through generalized linear model selection with 5-fold cross validation.
For hematological parameters, the optimal cutoffs to predict efficacy were determined using X-tile[1]. And multivariate Cox regression was conducted to identify independent biomarkers.
The clinical efficacy data cutoff date was June 13, 2022.
Results
Serum Proteomics
Proteomic profiling results were obtained from 168 patients (128 in the serplulimab group and 40 in the placebo group). The proteomic profiles were compared between responders and non-responders in the serplulimab group, and 181 DEP were identified. To further select the protein signature, investigators divided the patients into a training set (80 in the serplulimab group) and a validation set (48 in the serplulimab group and 40 in the placebo group). A generalized linear model selection with 5-fold validation was applied on the training set use 181 DEP and 15-protein signature was selected, which can sufficiently predict the responders from non-responders in the serplulimab group.
The predictive model based on the 15-protein signature showed an AUC of 0.982 in the training set, and 0.918 and 0.545 in the validation sets for the serplulimab and the placebo groups, respectively. Patients with high signature scores, which were generated from the protein set analysis of the 15-protein signature, derived benefits from adding serplulimab to chemotherapy in terms of PFS and OS (Table 2 and Figure 2), while those with low signature scores did not appear to derive benefits.
Genomic Mutations
Genetic mutation data were available for 305 patients. After excluding 3 outliers, 302 patients were included in the analysis. Patients with mutations in the RB1 gene or the NOTCH pathway had higher response rates to serplulimab-chemotherapy compared with those without mutations (Table 3). While Patients with RB1 mutations and treated with serplulimab-chemotherapy had a tendency towards longer PFS and OS (Figure 3).
Hematological Parameters
Among all 585 patients, 583 had available test results for NLR and PLR, while 582 had available test results for LDH. The analysis results indicated that high levels of baseline NLR, PLR, and LDH level were correlated with shorter PFS and OS in both treatment groups (Figure 4), implicating these are potential prognostic biomarkers for SCLC and correlate with poor patient prognosis.
In the univariate Cox regression model, NLR, PLR and LDH levels were associated with patient outcomes in SCLC, while the multivariate Cox regression model showed that baseline NLR and LDH level were independent prognostic biomarkers (Table 4).
Conclusion
Although several treatments of immunotherapy plus chemotherapy have been approved for the treatment of small cell lung cancer (SCLC), biomarkers to predict immunotherapy for SCLC are not well characterised. There is an urgent need to identify reliable biomarkers that can predict elaborate biological characteristics of the ES-SCLC patients who can benefit from the treatment, further improving survival in SCLC patients.
Our results showed that a 15-protein signature score exhibited potential as a predictive biomarker for the efficacy of serplulimab plus chemotherapy. Additionally, mutations in the RB1 gene and the NOTCH pathway were associated with a more favorable treatment response to serplulimab plus chemotherapy (due to the limited sample size, the above results need further validation in clinical studies). Furthermore, high baseline NLR and LDH correlate with poor prognosis, suggesting that baseline NLR and LDH were independent prognostic biomarkers for ES-SCLC. These findings shed light on the potential of new biomarkers for immunotherapy plus chemotherapy in patients with ES-SCLC, which warrant further investigation.
Reference
1. Camp R L, et al. Clin Cancer Res. 2004;10:7252–7259.
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 Indonesia. 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. Focus 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 3,900 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 the 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.
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Privacy Policy
Introduction
Shanghai Henlius Biotech, Inc., and, where applicable, its affiliates and subsidiaries (collectively, “we” , “us” or “our”) attach great importance to the protection of your privacy and personal information. This Privacy Notice (this “Policy”) is formulated in accordance with applicable PRC laws and regulations governing the protection of personal information in the People’s Republic of China (“PRC”).
This Policy applies when: (1) you browse or use our website and other online resources (such as our WeChat official accounts); (2) subscribe to our news or announcements; or (3) contact us through the contact details or other interactive features made available on our website, or otherwise interact with us through our website.. The purpose of this Policy is to explain how and why we process your personal information, the types of personal information involved, applicable retention periods, your rights, and the measures we take to protect personal information. Please read this Policy carefully to ensure that you fully understand its content.
In certain business scenarios, we may provide additional explanations regarding the processing of your personal information through separate agreements, privacy statements, or personal information notices. In the event of any inconsistency, such documents shall prevail. For example, where a recruitment function is provided through a third-party platform or service, the relevant third party privacy policy or notice may also apply.
For the purposes of this Policy, “personal information” refers to all kinds of information related to identified or identifiable natural persons, excluding anonymized information.
We collect, use, store, transfer and otherwise process personal information in strict compliance with applicable PRC laws and regulations of the People’s Republic of China.
Our website may contain links to third party websites for your convenience. We do not control, and are not responsible for, the privacy practices of such third parties. We encourage you to review their privacy policies before using those websites.
If you have any questions or concerns regarding this Policy or our processing of personal information, please contact us using the details provided below.
This Policy will help you understand:
I. How we collect your personal information
II. How we use your personal information
III. How we entrust, share, transfer and publicly disclose your personal information
IV. Cross border transfer of personal information
V. How we store your personal information
VI. Security measures
VII. Your rights
VIII. Personal information of minors
IX. Updates to this Policy
X. How to contact us
I. How do we collect your personal information?
In addition to our employees, we may process personal information of the following persons:
• Visitors and users of our website;
• Healthcare Professionals;
• Investigators of clinical trial institutions and personnel of contract research organizations in clinical trials;
• Subjects of clinical trials and their relatives;
• Consumers/patients and their relatives using our products or services;
• Staff of business partners (including vendors, distributors, partners, etc.); and
• Our applicants.
We may process personal information of website visitors and individuals who contact or interact with us through our website or other online resources. Depending on the relevant page, function, or interaction, separate privacy notices, consents, platform privacy policies, contracts, or other notices may apply.
Based on the context in which you interact with us, we may collect personal information by the following means and on the legal bases permitted by applicable PRC laws and regulations, including your consent, the necessity for entering into or performing a contract, compliance with legal obligations, protection of life, health or property, public health needs, or other circumstances permitted by law:
• Your personal information provided to us voluntarily
When you subscribe to our news or announcements, contact us through the contact details or other interactive features made available on our website, a third-party platform or service linked or referred to on our website, or otherwise communicate with us in relation to our website, we may collect the personal information that you voluntarily provide, such as your name, contact details, organization, and the content of your inquiry or request, depending on the relevant page or function.
• Personal information collected by us independently through our website and other online channels
When you visit our website, most of our services do not require any registration, and you can visit our website without telling us who you are. However, some pages or functions may require you to provide certain personal information. If you choose not provide such information as we request, you may not be able to access certain content or functions or we may not be able to respond to your inquiry, request or subscription. Please refer to the relevant page or notice for further details about the categories of personal information collected in a specific scenario.
• Personal information we collect from vendors or business partners
In the course of our daily business operations, we may collect personal information from our vendors or business partners. We require our vendors and business partners to comply with the requirements of the personal information protection laws and regulations of the PRC and to lawfully provide us with personal information. If you are an employee or representative of one of our vendors or business partners, we may collect personal information such as your name and contact details for the purpose of establishing business contacts and cooperations.
• Personal information we collect from publicly available sources
We may collect personal information of medical and healthcare professionals from such publicy available sources, such as the official websites of medical institutions and the official websites of competent government departments, and process such information within a reasonable scope and for lawful purposes. For example, for the purpose of lawful academic or professional interaction with healthcare professionals, we may collect the name, gender, employer, position, practitioner registration information, academic title, degree, educational background, specialty expertise, and profile information, where such information has been lawfully made public.
Our website may include links, contact details, QR codes, or references to third-party platforms or services. Where you choose to interact with us through such third-party platforms or services, the relevant third party may also process your personal information in accordance with its own privacy policy and applicable law, and we encourage you to review such policy before submitting your information.
II. How do we use your personal information?
We may use your personal information for the following purposes:
• Operating, maintaining and improving our website and other online resource;
• Researching, developing, providing and continuously improving our products and services;
• Conducting and managing daily business;
• Academic interaction with healthcare professionals;
• Responding to your inquiries, requests, or communications sent through our website or the contact details made available on our website;
• Providing subscription services for our news, announcements, or investor-related updates;
• Managing and maintaining our relationship and communications with business contacts who reach us through our website;
• Recruiting and human resource management;
• Internal compliance management，audit，record-keeping; and
• Complying with applicable PRC laws and regulations, for example, monitoring and reporting adverse events for purposes of performing drug quality management responsibilities, providing medical information and dealing with product complaints, etc..
We will process personal information only to the extent necessary for the relevant purpose. Where required by applicable law, we will obtain your consent or separate consent before processing your personal information or sensitive personal information. Where a third-party platform or service is used in connection with a particular function, the relevant third party may process your personal information in accordance with its own privacy policy and applicable law.
III. How do we entrust, share, transfer and publicly disclose your personal information?
1. Entrustment
We may entrust our business partners with the processing of your personal information for the purpose(s) described in this Policy. We will enter into appropriate confidentiality, data processing and security agreements with such entrusted parties and require them to process personal information in accordance with our instructions , this Policy and applicable PRC laws and regulations.
2. Sharing and public disclosure
For the purpose(s) described in this Policy, we will share or publicly disclose your personal information only where permitted by applicable PRC laws and regulations and, where required, after obtaining your consent or separate consent. Such circumstances may include:
• Sharing your personal information among our affiliates and subsidiaries where necessary for legitimate business, management, compliance, or operational purposes;
• Sharing your personal information with vendors or business partners (such as conference service providers, travel service providers, data service providers, banking or insurance institutions, other professional service organizations, to the extent necessary for the relevant purpose); and
• Disclosing your personal information to the extent that it is permitted or required by applicable PRC laws and regulations or for the purpose of assisting with investigations by judicial, regulatory or law enforcement authorities.
• other circumstances permitted by applicable PRC laws and regulations.
If you submit your information through or in connection with a third-party platform or service referred to on our website, the relevant third party may independently process your personal information in accordance with its own privacy policy and applicable law.
3. Transfer
We will not transfer your personal information to any other company, entity or individual unless otherwise permitted by applicable law and, where required, after obtaining your consent. Further, in the event of a merger, acquisition, insolvency, reorganization, division, dissolution, bankruptcy, or similar transaction, we will require the new processor of your personal information to continue to be bound by this Policy or we will require the new processor to obtain your consent again.
IV.How do we provide your personal information across borders?
In principle, personal information that we collect and generate in the course of our operations within the territory of the PRC will be stored within the PRC. In certain circumstances, it may be necessary for us to provide your personal information to recipients outside the PRC in connection with our business operations, website functions, or communications, where permitted by applicable PRC laws and regulations. As required by applicable laws and regulations regarding the protection of personal information, we will provide you with the required notice and obtain your separate consent before providing your personal information across any border, unless otherwise permitted by law. We will use lawful cross-border transfer mechanisms to transfer your personal information oversea and will take necessary measures to ensure that the oversea recipients provide a level of protection required by applicable PRC laws and regulations.
You may obtain more information about cross-border transfers of personal information and oversea recipients through the contact methods referred to in this Policy.
V. How do we store your personal information?
We will retain your personal information for the minimum period necessary to achieve the purposes described in this Policy ,unless a longer retention period is required or permitted by applicable PRC laws and regulations. Upon expiration of the applicable retention period, we will promptly delete or anonymize your personal information in accordance with applicable PRC laws and regulations. Our criteria for determining the period for which personal information shall be retained include:
• Applicable laws, regulations and other relevant requirements;
• The period of time needed for us to provide services, maintain business relations or interact with you; and
• The period of time needed for us to perform relevant agreements or fulfil the purposes described in this Policy.
VI. What security measures do we take to protect your personal information?
In accordance with applicable PRC laws, regulations, and the requirements of relevant national standards, we take reasonable and appropriate security and precautionary measures to protect the personal information we process against unauthorized access, public disclosure, use, modification, destruction or loss of data. However, you are also responsible for taking appropriate measures to protect the security of the devices, systems, and networks you use when accessing our website or communicating with us.
VII. Your rights
In accordance with the requirements of the applicable PRC laws and regulations, you may have the following rights in respect of your personal information:
• To know about and make decisions regarding the processing of your personal information;
• To access or copy your personal information;
• To correct or supplement your personal information;
• To delete your personal information;
• To request for explanation of rules regarding processing of personal information; and
• To change the scope of your consent or revoke your consent , where processing is based on your consent.
If you wish to exercise your rights with respect to personal information, you may contact us through the contact information listed in this Policy and we will respond to any request in accordance with applicable relevant laws and regulations. When you exercise the above rights, we may verify your identity to safeguard the security of your personal information. Subject to applicable PRC laws and regulations, there may be circumstances where we are unable to respond to all or part of your request.
VIII. How do we process the personal information of minors?
For the purposes of this Policy and in accordance with applicable PRC laws and regulations, our products, websites and services are not targeted at minors under the age of 14. Minors under the age of 14 should not provide personal information to us without the consent of a parent or legal guardian.
If a minor's personal information is collected with the consent of a parent or legal guardian, we will process the information only when permitted by law, with the express consent of the parent or legal guardian, or necessary for the protection of the minor. If we discover that we have collected personal information without obtaining verifiable prior consent of a parent or legal guardian, we will seek to delete the data as soon as possible.
IX. Updates of the Policy
We may revise our Privacy Policy from time to time. We will post the updated version on our website and update the “Last Updated” date above or below this Policy.
Last updated: March 30, 2026.
X. How to contact us?
If you have any questions, comments or suggestions concerning this Policy, or any questions or concerns about our processing of your personal information, you may contact us in the following ways:
Address: 11/F, B8 Building, No.188 Yizhou Rd, Xuhui District, Shanghai
Tel.: 021- 33395800
Postal Code: 200233
Email: PR@178xian.com
Cookies Policy
When you visit our website, we may place small data files known as “cookies” on your device. Cookies enable our website to recognize your browser and help us understand how visitors use the site.
Cookies and similar technologies used on this website may collect online identifiers, device information, browser information, IP address, and information about how you interact with the website. In certain circumstances, such information may constitute personal information or may be associated with you under applicable PRC laws and regulations. Information collected through cookies is used for purposes such as ensuring website operation, maintaining security, analyzing traffic and performance, remembering user preferences, and improving website content and user experience.
You may choose to accept or decline cookies by adjusting your browser settings or through any cookie banner or preference center made available on our website, if applicable. Please note that disabling cookies may affect the functionality of certain parts of the website.
For more information about how we process personal information, please refer to our Privacy Notice.
Some cookies may be provided by third parties. Where third-party cookies or similar technologies are used, such third parties may process the relevant information in accordance with their own privacy policies and applicable PRC laws and regulations.
Accessibility
Shanghai Henlius Biotech, Inc. (“Henlius”) is committed to improving the accessibility and user friendliness of its website for all visitors.
We strive to ensure that the content on our website can be accessed and used by individuals with diverse needs, including those who rely on assistive technologies. As our website continues to evolve, we recognize that accessibility is an ongoing effort, and we are continuously working to improve usability and accessibility across our digital platforms.
If you experience difficulty accessing any part of our website, or have suggestions on how we can enhance accessibility, we welcome your feedback. To help us respond effectively, please include the specific webpage address (URL) and a brief description of the issue encountered.
Contact us:
Email: PR@178xian.com
(Please include “Website Accessibility” in the subject line)
Henlius will make reasonable efforts to review accessibility-related feedback and improve the overall online experience for all users. While we strive to improve accessibility, we do not guarantee that every page or feature will be fully accessible to every user in all circumstances.
Terms of Use
This website (http://www.178xian.com/) is developed and operated by Shanghai Henlius Biotech, Inc. (“Henlius”). Please read these Terms of Use carefully before accessing or using this website. By accessing, browsing or using this website, you acknowledge that you have read, understood and agreed to be bound by these Terms of Use and applicable PRC laws and regulations.
Henlius reserves the right to modify or update these Terms of Use at any time. Any updated version will be posted on this website with a revised “Last Updated” date. Please review them periodically for updates.
Prohibited Conduct:
You shall not infringe the lawful rights and interests of Henlius or any third party, nor interfere with or attempt to interfere with the normal operation, security, or integrity of this website by any means. Without limitation, you shall not use this website for any unlawful purpose, attempt unauthorized access to any part of the website or related systems, introduce malicious code, scrape or extract website content through automated means, or otherwise interfere with the website’s operation or security features.
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You use this website and any information obtained from it at your own risk. To the fullest extent permitted by applicable PRC laws and regulations, Henlius shall not be liable for any loss or damage arising from the use or inability to use this website, including but not limited to system failures, computer viruses or data loss.
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Henlius respects your privacy. Please refer to our Privacy Notice for details.
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Last updated: March 30, 2026
