Shanghai, China, September 9, 2024 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the latest results of the company’s self-developed innovative anti-PD-1 monoclonal antibody (mAb), HANSIZHUANG (serplulimab) were released as poster presentations at 2024 World Conference on Lung Cancer (“WCLC 2024”) in the field of small cell lung cancer (SCLC).
HANSIZHUANG, the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC, has been launched in China, Indonesia, Cambodia and Thailand. Up to date, it has been approved by the National Medical 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), broadly covering high-incidence tumours including lung cancer and gastrointestinal cancer, benefiting about 80,000 patients.
Lung cancer is one of the most common malignancies around the world. SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases[1]. The SCLC breaks down into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. To date, HANSIZHUANG has been approved for the first-line treatment of ES-SCLC in China, Indonesia, Cambodia and Thailand. Its Marketing Authorisation Application (MAA) for ES-SCLC has been validated by the European Medicines Agency (EMA), which is expected to be approved in 2024. In the meantime, Henlius has successively conducted a number of immuno-combination therapy clinical trials with serplulimab, including several global multi-centre phase 3 clinical trials regarding sqNSCLC, ES-SCLC and LS-SCLC, covering the full range of first-line treatments of lung cancer. Henlius has also initiated a head-to-head bridging 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.
The latest data of the studies released at 2024 WCLC conference are as follows:
ASTRUM-005R
Title
Real-world First-line Serplulimab-based Immunochemotherapy for Extensive-stage Small Cell Lung Cancer: The Multicenter ASTRUM-005R Study
Study design
This cohort study enrolled adult patients with ES-SCLC at 14 institutions in China from April 2022 to April 2024. These patients received at least two cycles of first-line serplulimab combined with chemotherapy and underwent at least one response assessment. The primary endpoint was the investigator-assessed real-world progression-free survival (rwPFS) according to RECIST version 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety profiles refer to CTCAE version 5.0.
Results
A total of 538 patients were enrolled and evaluated for both efficacy and safety. The participants had a median age of 63 years (range 57.00-68.75), with 467 (86.80%) being male and 406 (75.46%) having a history of smoking. Most patients (491, 91.26%) had an ECOG PS of 0 or 1. Comorbidities, excluding other primary tumors, were present in 44.05% (237 patients). Liver and brain metastases were observed in 33.09% (n=178) and 21.56% (n=116), respectively. The median number of immunochemotherapy cycles was 4 (range 4-6), with 41.26% (n=222) receiving more than four cycles. The median rwPFS was 9.1 months (95% CI 8.1-9.7), with a 1-year rwPFS rate of 34.6%, surpassing the 1-year PFS rate of 28.2% reported for the Asian in the ASTRUM-005 study. Besides, the 2-year rwPFS rate was shown to be 11.3%. The median rwPFS was 9.7 months (95% CI 8.8-12.8) in patients without liver metastasis, significantly longer than the 7.4 months (95% CI 6.2-8.9) in patients with liver metastasis (P < 0.0001). Patients who received >4 cycles of immunochemotherapy had a median rwPFS of 10.5 months (95% CI 9.3-13.3), which was significantly longer than the 6.7 months (95% CI 6.3-9.1) in patients who received ≤4 cycles (P < 0.0001). The OS was not yet mature, and the ORR was 71.29%. The occurrence frequency of adverse event of special interest (AESI) was 38.85% (421 events), in which grade ≥3 AESIs occupied 15.43%.
Conclusion
The ASTRUM-005R study provides additional empirical evidence to support the therapeutic value of serplulimab plus chemotherapy and complements the pivotal data from the ASTRUM-005 clinical trial.
A retrospective study
Title
Is neoadjuvant chemoimmunotherapy better than chemotherapy in patients with limited-stage small cell lung cancer: a retrospective comparative study
Study design
Patients with LS-SCLC who received neoadjuvant PD-L1/PD-1 inhibitor plus platinum-based chemotherapy or platinum-based chemotherapy alone followed by surgery between Jan 2018 and Oct 2023 in our institute were included. The primary endpoints were pathologic complete response rate and major pathologic response. The second endpoints were R0 resection rate, downstaging rate and disease-free survival.
Results
Of the 51 eligible patients, 26 received neoadjuvant chemoimmunotherapy and 25 received neoadjuvant chemotherapy (Table 1). There were 39 males and 12 females across both groups combined. Mean (range) age at diagnosis was 61.6 years (43.1-74.5) for the chemoimmunotherapy group and 59.5 years (45.8-73.2) for chemotherapy group. Pathologic complete response rate was 38.5% (10/26) in chemoimmunotherapy group versus 8.0% (2/25) in chemotherapy group (OR 7.2, 95% CI 1.4-37.3) (Table 2). Major pathologic response rate was 53.8% (14/26) in chemoimmunotherapy group versus 12.0% (3/25) in chemotherapy group (OR 8.6, 95% CI 2.0-35.8). R0 resection rate was 92.3 (24/26) in chemoimmunotherapy group versus 80.0% (20/25) in chemotherapy group (OR 3.0, 95% CI 0.5-17.2). Pathologic downstaging rate (88.5% vs 36.0) and N2 downstaging rate (68.2 vs 24.0) were higher in chemoimmunotherapy group. After a median follow up of 17.2 months, median DFS was not reached in chemoimmunotherapy group versus 11.3 (95% CI, 6.1-16.5) months in chemotherapy group.
Conclusion
Neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy demonstrated promising efficacy and feasibility, and are a potential strategy for the management of LS-SCLC. Further prospective randomized controlled trials are necessary to clearly define the benefit of neoadjuvant chemoimmunotherapy and optimize LS-SCLC treatment.
【Reference】
[1] Eskandar A, Ahmed A, Daughtey M, et al. Racial and sex differences in presentation and outcomes of small cell lung cancer in the United States: 1973 to 2010[J].Chest, 2015,147(4): e164-e165.
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. 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.