On June 6, 2022, Fuhong Henlin (2696. HK) announced that the company's first innovative monoclonal antibody H drug Hans-like ® (slullimonumab) international multicenter Phase III clinical study (ASTRUM-005) for first-line extensive stage small cell lung cancer (ES-SCLC) was orally presented by the lead investigator Professor Cheng Ying of Jilin Provincial Cancer Hospital at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
This is also the first time that China's self-developed anti-PD-1 monoclonal antibody has been reported at the ASCO Annual Meeting in the form of oral reports in the field of first-line lung cancer, which fully demonstrates the leading R&D capabilities and international clinical operation strength of Chinese pharmaceutical enterprises in innovative biological drugs.
Professor Cheng Ying said, "The ASTRUM-005 study is the first international multicenter clinical study of the largest PD-1 inhibitor for widespread small cell lung cancer led by Chinese researchers, with subjects from 114 research centers around the world participating in the screening, enrolling more than 31.5% of Caucasian races. The results of the study showed that the median total survival of Slullizumab combined with chemotherapy in the first line treatment of wide-stage small cell lung cancer was 15.4 months, which was significantly improved compared with the control group, and was internationally recognized, and the immunotherapy for small cell lung cancer achieved a new leap. ”
Zhu Jun, president of Fuhong Henlius
He said: "H drug is an innovative monoclonal antibody product independently developed by Henlius Fuhong, and we have focused on the unmet needs of patients and made a comprehensive layout in the field of frontline lung cancer. At present, the company's application for market registration for SCLC has been accepted by the State Food and Drug Administration, and H drug is expected to become the world's first-line treatment of SCLC anti-PD-1 monoclonal antibody. It is hoped that this indication will be approved as soon as possible, fill the clinical gap as soon as possible, and provide new treatment options for patients with small cell lung cancer worldwide. We will continue to expand more treatment options needed clinically, and benefit patients around the world from the research results of Chinese biopharmaceuticals. ”
ASTRUM-005 has opened a total of 128 test centers in China, Turkey, Poland, Georgia and other countries, of which 114 test centers have participants in the screening, a total of 585 subjects, of which about 31.5% are Caucasians. Sufficient international clinical trial data is also expected to support the declaration of H drug in the EUROPEAN Union, the United States and other mainstream regulatory markets, laying a foundation for global clinical applications. The results of the published trial are as follows:
Thesis title
Comparison of innovative anti-PD-1 antibody Slullizumab combined chemotherapy with chemotherapy alone in the first-line treatment of extensive small cell lung cancer: an international, randomized Phase III clinical study (Abstract No. 8505)
experimental design
This study is a randomized, double-blind, international multicenter, Phase III clinical study comparing the efficacy and safety of slullizumab plus chemotherapy (carboplatin-etoposide) and placebo combination chemotherapy (carboplatin)) in patients with previously untreated ES-SCLC. The included patients were randomly divided into two groups on a 2:1 ratio, receiving intravenous slulizumab or placebo combination chemotherapy every three weeks until disease progression, death, toxic intolerance, withdrawal of informed consent from the subject, or other conditions specified in the regimen (whichever occurs first). The primary endpoint of the study was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic profile, and immunogenicity.
outcome
As of October 22, 2021, the study enrolled a total of 585 eligible patients (slullizumab group, n=389; placebo group, n=196), with a median follow-up time of 12.3 months. The median OS of the Srullimonumab and placebo groups was 15.4 months (95% CI 13.3–NE) and 10.9 months (95% CI 10.0–14.3), respectively, and the risk ratio (HR) was 0.63 (95% CI 0.49–0.82; p). <0.001）。 The 24-month overall survival rates for the two groups were 43.1% and 7.9%, respectively. The median PFS of the Slullimonumab and placebo groups assessed by the Independent Imaging Evaluation Board (IRRC) under RECIST v1.1 were 5.7 and 4.3 months (HR 0.48, 95% CI 0.38–0.59), respectively. Improvements in efficacy were also observed in IRRC assessments of ORR (80.2% vs. 70.4%) and DOR (median DOR, 5.6 vs. 3.2 months) based on RECIST v1.1.
In 129 (33.2%) and 54 (27.6%) patients in both trial groups, respectively, experienced treatment-related adverse events (TRAEs) of grade III or above related to srullimonumab or placebo. The incidence of immune-related adverse events (irAEs) was higher in the srullizumab group than in the placebo group and similar to the approved PD-1/PD-L1 monoclonal antibody.
conclusion
The experimental results show that srullimonumab combined with carboplatin-etoposide can significantly improve the OS of patients with first-line ES-SCLC, and its safety is consistent with the previous research results. Slulizumab is expected to be the world's first-line anti-PD-1 monoclonal antibody product for the first-line treatment of ES-SCLC, providing a new treatment option for such patients.
About H drug Hans-like ®
H drug Hans is ® a recombinant humanized anti-PD-1 monoclonal antibody injection (generic name: slullimonumab injection), which is the first innovative monoclonal antibody independently developed by Henlin Fuhong, and currently 1 indication has been approved for marketing, 2 indications have been accepted for marketing, and 9 clinical trials have been carried out simultaneously worldwide.
In March 2022, H drug was officially approved for the treatment of microsatellite highly unstable (MSI-H) solid tumors. Focusing on H medicine, Henlius actively promotes its synergy with other products of the company and the combination of innovative therapies, and has successively obtained clinical trial licenses from China, the United States, the European Union and other countries and regions, and carried out 9 clinical trials of combination therapies for tumor immunity in the world, covering a wide range of indications such as lung cancer, esophageal cancer, head and neck squamous cell carcinoma and stomach cancer, and comprehensively covering the first-line treatment of lung cancer. Up to now, H drug has enrolled more than 2800 people in China, Turkey, Poland, Georgia and other countries and regions, of which 2 international multi-center clinical trials have enrolled more than 30% of Caucasian races, which is one of the anti-PD-1 monoclonal antibodies with more international clinical data. H-drug combination chemotherapy for locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) and first-line treatment of extensive small cell lung cancer (ES-SCLC) have been accepted by NMPA and selected as ES-SCLC treatment recommendations in the 2022 CSCO Small Cell Lung Cancer Guidelines. In addition, its treatment of small cell lung cancer (SCLC) has also been certified as an FDA orphan drug. The company also plans to apply for ES-SCLC listing in the European Union in 2022, which is expected to become the world's first-line treatment of SCLC's anti-PD-1 monoclonal antibody. In the field of first-line treatment of esophageal squamous cell carcinoma, the H-drug combination chemotherapy phase III study has also reached the two main study endpoints.
About Henlius
Fuhong Henlin (2696. HK) is an international innovative biopharmaceutical company, committed to providing affordable high-quality biopharmaceuticals for patients around the world, covering oncology, autoimmune diseases, ophthalmic diseases and other fields, has been listed in China 5 products, 1 product listed in Europe, 13 indications approved, 2 listing registration applications accepted by the China Food and Drug Administration. Since its establishment in 2010, Henlius has built an integrated biopharmaceutical platform with efficient and innovative independent core capabilities running through the entire industry chain of R&D, production and commercial operation. The company has established a perfect and efficient global innovation center, in accordance with the international good manufacturing practice (GMP) standards for production and quality control, and constantly consolidate the integrated integrated production platform, of which, Shanghai Xuhui base has obtained China and EU drug GMP certification, Songjiang base (1) has also obtained China GMP certification.
Henlius has prospectively laid out a diversified, high-quality product pipeline covering more than 20 innovative monoclonal antibodies and comprehensively promoted Hans-like ® combination therapy for tumor immunology based on its own anti-PD-1 monoclonal antibody H drug. Following the first domestic biosimilar Hanlikang ® (rituximab), China's first independently developed Sino-European double-batch monoclonal drug HanQuyou ® (trastuzumab, European trade name: Zercepac®), Handayuan ® (adalimumab) and Hamperite ® (bevacizumab) have been approved for listing, and the innovative hans-like ® (slullizumab) has been approved for the treatment of microsatellite highly unstable (MSI-H) solid tumors. Its application for marketing registration for two indications, squamous non-small cell lung cancer and extensive small cell lung cancer, is also under review. The company has also carried out more than 20 clinical trials around the world on 12 products and 10 immune combination treatment programs, and has authorized a comprehensive coverage of the mainstream biological drug market in Europe and the United States and many emerging markets.
ASTRUM-005 | Henlius Released Phase 3 Study Results for the First-line Treatment of Small Cell Lung Cancer of Serplulimab at ASCO 2022
Shanghai, China, June 6th, 2022 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that an international randomized phase 3 study (ASTRUM-005) of HANSIZHUANG (serplulimab), an anti-PD-1 mAb independently developed by Henlius, as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) has been orally presented at 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Serplulimab is the first China-developed anti-PD-1 mAb in first-line treatment of lung cancer that was presented orally at ASCO Annual Meeting. The leading principal investigator is Professor Ying Cheng from Jilin Cancer Hospital.
Professor Ying Cheng said,"ASTRUM-005 is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. A total of 114 sites’ subjects were screened around the globe, with 31.5% being Caucasian. The study results demonstrated that serplulimab in combination with chemotherapy can significantly extend the median OS to 15.4 months when compared to the control group in first-line SCLC, gaining global recognition while leapfrogging immunotherapy treatment for SCLC patients.”
Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius. Based on the large number of unmet clinical needs, the company has implemented a comprehensive first-line treatment strategy for lung cancer with multiple clinical trials. Previously, the NDA of HANSIZHUANG for the treatment of ES-SCLC has been accepted by NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. We are hoping that the approval comes soon to mend the gap and bring a new treatment option to patients living with ES-SCLC. Going forward, we will proactively promote more clinical research, thereby benefiting more patients around the world."
ASTRUM-005 has set up a total of 128 sites in China, Turkey, Poland, Georgia, etc. and enrolled 585 subjects from 114 sites, among whom 31.5% were Caucasian. In December 2021, ASTRUM-005 had met its primary study endpoint of the overall survival (OS) in the interim analysis and demonstrated HANSIZHUANG with a manageable safety profile. The global clinical data lays a solid foundation for future applications across the world. ASTRUM-005 results are as follows:
Titile
Serplulimab, a novel anti-PD-1 antibody, plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small-cell lung cancer: An international randomized phase 3 study (Abstract No. 8505)
Study design
This randomized, double-blind, international, multicenter, phase 3 clinical study aimed to compare the efficacy and safety of serplulimab with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with ES-SCLC. Enrolled patients were randomized 2:1 to receive intravenous infusion of either serplulimab or placebo in combination with chemotherapy every three weeks until disease progression, death, intolerable toxicity, withdrawal of informed consent or other reasons specified in the protocol (whichever occurred first). The primary endpoint of this study was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic characteristics, and immunogenicity.
Results
As of October 22, 2021, 585 eligible patients were randomized (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. The median OS in the serplulimab group and the placebo group were 15.4 (95% CI 13.3–NE) and 10.9 (95% CI 10.0–14.3) months, respectively, with a hazard ratio (HR) of 0.63 (95% CI 0.49–0.82; p<0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median PFS assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was 5.7 months in the serplulimab group and 4.3 months in the placebo group (HR 0.48, 95% CI 0.38–0.59). Efficacy improvements were also observed in ORR (80.2% vs. 70.4%) and DOR (median, 5.6 vs. 3.2 months) as assessed by IRRC per RECIST v1.1.
Grade ≥3 treatment related adverse events (TRAEs) related to serplulimab or placebo were reported by 129 (33.2%) and 54 (27.6%) patients in the respective groups. Incidence of immune-related adverse events (irAEs) was higher in the serplulimab group compared to the placebo group (37.0% vs. 18.4%), and was similar to the approved PD-1/PD-L1 antibodies.
Conclusions
The results demonstrated that serplulimab in combination with carboplatin-etoposide significantly improved OS as first-line treatment in ES-SCLC patients. The safety profile was consistent with previous studies. Serplulimab, as the first anti-PD-1 antibody showing OS benefit in untreated ES-SCLC patients, possess the potential to provide an alternative treatment option for this patient population worldwide.
About HANSIZHUANG
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 2 NDAs have been accepted by the NMPA, and 9 clinical trials are ongoing across the world.
HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and the first-line treatment of extensive small-cell lung cancer (ES-SCLC) have been accepted by the NMPA. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC. The MAA of ES-SCLC is expected to be filed in the EU in 2022, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. In the field of esophageal squamous cell carcinoma, the phase 3 clinical trial of HANSIZHUANG in combination with chemotherapy has met the co-primary endpoints.
About Henlius
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 in Europe, 13 indications approved worldwide, and 2 New Drug Application (NDA) accepted for review in China. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name in Europe: Zercepac®), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors and its NDA for the treatment of squamous non-small cell lung cancer and extensive small-cell lung cancer (ES-SCLC) are under review. What's more, Henlius has conducted over 20 clinical studies for 12 products and 10 combination therapies.
Contact details
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