The world's first clinical study of small cell lung cancer immunotherapy listed in the international top journal JAMA, H drug Hans-like combination chemotherapy first-line ® treatment of extensive small cell lung cancer positive results were released

On September 27, 2022, the international multicenter research led by Professor Cheng Ying, ASTRUM-005 research, one of the world's top four medical journals, Journal of the American Medical Association (JAMA, impact factor: 157.
3), was published online, becoming the world's first clinical study
of small cell lung cancer immunotherapy to be published in the main journal of JAMA.
ASTRUM-005 research is Fuhong Henlius independently developed anti-PD-1 monoclonal antibody H drug Hansi-like (sluliumab) combined with chemotherapy first-line treatment of extensive stage small cell lung cancer (ES-SCLC ^®) Phase III clinical research, 2022 ASCO annual meeting Professor Cheng Ying reported the results for the first time, has attracted widespread attention from global peers, and now once again on the international top academic stage, reflecting the high recognition of the international academic community, It highlights the wisdom of Chinese researchers and the world-class independent innovation strength and clinical operation ability
in the field of biomedicine.

A link to the full text is available at the end of the article

Professor Cheng Ying

Corresponding author and first author, Professor Cheng Ying of Jilin Provincial Cancer Hospital, the principal investigator of the ASTRUM-005 study, said:

The ASTRUM-005 study of slulizumab combined with chemotherapy obtained the longest OS result in the current first-line immunotherapy for generalized small cell lung cancer, which can extend survival by 4.
5 months compared with chemotherapy, the lowest HR to date: 0.
63, and the results of short-term and long-term efficacy are consistent, and there is good safety at
the same time 。 This study is the first to confirm that PD-1 inhibitors combined with chemotherapy can also improve the survival of generalized small cell lung cancer, which is also the first international multi-center clinical phase III study for ES-SCLC indication immunotherapy led by our Chinese researchers, which fully demonstrates the strength of
Chinese researchers.
Thanks to the cooperation of all patients and families who contributed to the study, as well as the efforts of other researchers, this study has opened a new page for first-line immunotherapy for broad-stage small cell lung cancer, bringing good news
to the majority of patients.

OS reached 15.
4 months, setting a new record for the total survival of first-line small cell lung cancer

Small cell lung cancer (SCLC), which accounts for about 15% of the total number of lung cancers, is the most aggressive subtype of lung cancer, divided into limited-stage small cell lung cancer (LS-SCLC) and ES-SCLC
.
The common denominators of the two are high degree of malignancy, early metastasis, rapid disease progression, and poor overall prognosis
.
In recent years, the emergence of immune checkpoint inhibitors has brought new hope for the treatment of ES-SCLC field, anti-PD-L1 monoclonal antibody combined chemotherapy has been recommended as a first-line treatment regimen for ES-SCLC by authoritative guidelines at home and abroad, which has improved the overall survival of patients to a certain extent compared with chemotherapy, but the degree of improvement is relatively limited, and more effective treatment plans
are still needed.

ASTRUM-005 is a randomized, double-blind, international multicenter, phase III clinical study comparing the clinical efficacy and safety of H-drug combined chemotherapy and placebo combination chemotherapy in patients with ES-SCLC who have not received previous treatment, and has opened 128 trial centers in China, Turkey, the European Union, Poland, Georgia and other countries, of which 114 trial centers have subjects participating in screening, a total of 585 subjects in the group, about 31.
5% are white
。 As of October 22, 2021, the median follow-up time was 12.
3 months
for the slulizumab group (n=389) and placebo group (n=196) co-enrolled in this study.
The median OS in the slulizumab and placebo groups was 15.
4 months (95% CI 13.
3–NE) and 10.
9 months (95% CI 10.
0–14.
3), respectively, with a risk ratio (HR) of 0.
63 (95% CI 0.
49–0.
82; p<0.
001).

The 24-month overall survival rate for both groups was 43.
1% and 7.
9%,
respectively.
The median PFS assessed by the Independent Imaging Evaluation Committee (IRRC) against RECIST v1.
1 in the slulizumab and placebo groups was 5.
7 and 4.
3 months, respectively (HR 0.
48, 95% CI 0.
38–0.
59).

In terms of safety, the incidence of immunorelated adverse events (irAEs) in the slulizumab group was similar
to that of approved PD-1/PD-L1 monoclonal antibodies.

It is expected to benefit patients around the world and fill the clinical gap in the next five years

The success of the ASTRUM-005 study is a major breakthrough in the treatment of ES-SCLC with PD-1 inhibitors, based on which the State Drug Administration (NMPA) has accepted a marketing application for the first-line treatment of ES-SCLC indications for H drugs; The Guidelines for the Diagnosis and Treatment of Small Cell Lung Cancer in CSCO (2022 Edition) also added the Slulizumab Combined Chemotherapy EC Regimen as a first-line treatment recommendation for ES-SCLC, providing more options
for first-line treatment of ES-SCLC in China.
Not only that, the H drug for the treatment of SCLC was certified
as an orphan drug by the U.
S.
Food and Drug Administration (FDA) in April 2022.
At the same time, based on the positive feedback of the FDA on the marketing application for the treatment of H-drug ES-SCLC and the discussion results of the FDA's Class C consultation meeting, the company will launch a bridging clinical trial in the United States and intends to submit the corresponding listing application
in the United States by Q1 of 2024.
At present, no anti-PD-1 monoclonal antibody for first-line treatment of SCLC has been approved in the world, and H drug is expected to become the world's first anti-PD-1 monoclonal antibody for first-line treatment of SCLC, filling the clinical gap
of PD-1 inhibitors in the first-line treatment of small cell lung cancer in the next five years.

In the future, Henlius will continue to increase innovation, take clinical needs as the guide, and continue to efficiently provide more affordable and more effective treatment options for patients around the
world.

About JAMA

JAMA is a peer-reviewed, international, comprehensive medical journal with the primary goal
of promoting the science and art of medicine and improving public health.
Since its serial publication in 1883, JAMA has become one of the most influential journals in medicine and science, with a current impact factor of 157.
3
.
JAMA is also the world's most widely distributed comprehensive medical journal, with more than 290,000 print subscriptions, more than 1.
6 million online subscriptions, and more than 38 million annual visits to the journal website, with strong social media influence and international news media exposure
.

About H medicine Hans-like^®

H drug Hans is ^® a recombinant humanized anti-PD-1 monoclonal antibody injection (generic name: Slulimonomab injection), is Fuhong Henlius the first independent research and development of innovative monoclonal antibody, currently 1 indication has been approved for listing, 3 indications listing application has been accepted, 11 clinical trials simultaneously carried out
in the world.

In March 2022, H drug was officially approved for the treatment of microsatellite highly unstable (MSI-H) solid tumors
.
Focusing on H drugs, Henlius actively promotes its synergy with other products of the company and the combination with innovative therapies, and has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions, and has carried out 11 clinical trials of tumor immunotherapy in the world, covering a wide range of indications such as lung cancer, esophageal cancer, head and neck squamous cell carcinoma and gastric cancer, and comprehensively covering the first-line treatment of
lung cancer 。 Up to now, H drug has accumulated more than 3100 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 white people, which is one of
the anti-PD-1 monoclonal antibodies with more international clinical data.
The NDA of H drug combined with chemotherapy for squamous non-small cell lung cancer (sqNSCLC), extensive stage small cell lung cancer (ES-SCLC) and esophageal squamous cell carcinoma (ESCC) has been accepted by the NMPA, and H drug is expected to become the world's first anti-PD-1 monoclonal antibody
for first-line treatment of SCLC 。 In addition, the drug was selected as the "2022 CSCO Small Cell Lung Cancer Diagnosis and Treatment Guidelines" as the ES-SCLC treatment recommendation, and the international multi-center clinical study for ES-SCLC ASTRUM-005 became the world's first clinical study of small cell lung cancer immunotherapy on JAMA, and its treatment of small cell lung cancer (SCLC) has also been recognized as an orphan drug by
the US FDA.

About Henlius

Henlius Fuhong (2696.
HK) is an international innovative biopharmaceutical company, committed to providing affordable high-quality biological drugs 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 the international market, 13 indications approved, 5 listing registration applications accepted by the China Food and Drug Administration
.
Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform, with efficient and innovative independent core capabilities running through the entire industrial 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 production platform, of which, Shanghai Xuhui base has obtained Chinese and EU GMP certification, Songjiang base (I) has also obtained China GMP certification
.

Henlius Fuhong prospectively laid out a diversified and high-quality product pipeline, covering more than 20 kinds of innovative monoclonal antibodies, and comprehensively promoted the hans-like tumor immunocombination therapy
based on its own anti-PD-1 monoclonal ^® antibody H drug.
Following the first biosimilar in China, Hanlikang ^® (rituximab), China's first self-developed Sino-European double-batch monoclonal antibody drug Hantriyo ^® (trastuzumab, European trade name: Zercepac^®, Australian trade name: Tuzucip and Trastucip^®®), Handa Yuan ^® (Adalimumab) and Hambethai ^® (bevacizumab) have been approved for marketing, the innovative product Hansizumab (slullizumab ^®) has been approved for the treatment of microsatellite highly unstable (MSI-H) solid tumors, and its squamous non-small cell lung cancer, extensive stage small cell lung cancer and esophageal squamous cell carcinoma are also under review
。 The company has also simultaneously carried out more than 20 clinical trials on 13 products and 11 immunocombination therapy programs around the world, and fully covered the mainstream biopharmaceutical markets and many emerging markets
in Europe and the United States.

ASTRUM-005: The first immunotherapy clinical study of SCLC published in JAMA, one of the top medical journals in the world 

Shanghai, China, September 27^th, 2022 – Shanghai Henlius Biotech, Inc.
(2696.
HK) announced that ASTRUM-005, an international multi-centre study led by Professor Ying Cheng, has been published in The Journal of the American Medical Association (JAMA, impact factor of 157.
3), one of the top four medical journals in the world.
ASTRUM-005 trial is a phase 3 study of HANSIZHUANG (serplulimab), an anti-PD-1 monoclonal antibody (mAb) developed by Henlius independently, plus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC).
After Prof.
Ying Cheng orally presented them at the 2022 ASCO annual meeting, the results of ASTRUM-005 attract wide attention among the global research community.
And now, ASTRUM-005 makes its way to the international arena once again, demonstrating the high level of academic acclaim on a global scale, the intelligence of Chinese researchers, and the strength of Chinese pharmaceuticals in terms of independent innovation research and clinical development.

Prof.
Ying Cheng, the corresponding author and first author, as well as the leading principal investigator of the study, from Jilin Cancer Hospital, said, “In the ASTRUM-005 trial, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC.
Compared with chemotherapy, the treatment prolonged median OS by 4.
5 months and had the lowest HR of 0.
63.
In addition, the study showed good safety and consistent efficacy over time.
ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC.
It is also the first international multi-centre phase 3 clinical study led by Chinese researchers to employ immunotherapy for ES-SCLC treatment, showcasing the expertise and excellence of Chinese researchers.
I would like to thank all patients and their families, as well as researchers who contributed to this study.
It opens a new chapter in first-line ES-SCLC immunotherapy, which will benefit a large number of patients.
"

OS 15.
4 months, a new record

SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases.
Both limited stage SCLC (LS-SCLC) and ES-SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis.
The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC.
At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines at home and abroad as the first-line treatment for ES-SCLC.
Compared with chemotherapy, the overall survival (OS) of patients with SCLC has been prolonged to a certain extent, but the improvements were still modest, suggesting the need for more effective treatments in this patient population.

ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy in previously untreated patients with ES-SCLC.
ASTRUM-005 has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.
5% were White.
As of data cutoff for this interim analysis (October 22, 2021), 585 eligible patients were randomised (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.
3 months.
Median OS was significantly longer in the serplulimab group (15.
4 months, 95% confidence interval [CI] 13.
3-not evaluable) than in the placebo group (10.
9 months, 95% CI 10.
0-14.
3) (hazard ratio [HR] 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 progression-free survival assessed by an independent radiology review committee per RECIST v1.
1 was also longer in the serplulimab group compared to the placebo group (5.
7 months vs.
4.
3 months; HR 0.
48, 95% CI 0.
38-0.
59).
Incidence of immune-related adverse events (irAEs) was similar to the approved PD-1/PD-L1 antibodies.

Providing more treatment options for patients worldwide

The success of ASTRUM-005 is a breakthrough in the treatment of ES-SCLC with PD-1 inhibitors.
Based on the results of ASTRUM-005, the New Drug Application (NDA) of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA).
Furthermore, HANSIZHUANG has been recommended for the first-line treatment of ES-SCLC by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC.

In April 2022, the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of SCLC.
Based on the positive feedback from FDA Biologics License Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion on the FDA's Type C consultation meeting, Henlius is planning to soon carry out a bridging study in the US and expected to submit BLA to FDA before Q1 of 2024.
At present, there is no anti-PD-1 mAb approved for the first-line treatment of SCLC worldwide.
HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for the first-line treatment of SCLC and to fill the clinical gap in the next five years.

Looking forward, Henlius will actively improving efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.

About JAMA

JAMA, published continuously since 1883, is an international peer-reviewed general medical journal aiming to promote the science and art of medicine and the betterment of the public health.
JAMA (impact factor of 157.
3, one of the highest in medicine and science) is the most widely circulated general medical journal in the world, with more than 290,000 recipients of the print journal, more than 1.
6 million recipients of electronic tables of contents and alerts, and over 38 million annual visits to the journal's website.
JAMA's reach includes a growing social media presence and vast international news media exposure.

About HANSIZHUANG

HANSIZHUANG (recombinant humanised 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, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumours in March 2022 and its synergy with in-house products of the company and innovative therapies are being actively promoted.
It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 11 clinical trials on immuno-oncology combination therapies 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 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of White 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 first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.
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 the related clinical trial has also become the first study published in JAMA on SCLC immunotherapy.
Serplulimab was also granted orphan drug designation by the FDA for treatment of SCLC.

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 approved for marketing in overseas markets, 13 indications approved worldwide, and 5 New Drug Applications (NDAs) 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^®; trade names in Australia: Tuzucip^® and Trastucip^® ), 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 (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) are under review.
What's more, Henlius has conducted over 20 clinical studies for 13 products and 11 combination therapies, expanding its presence in major markets as well as emerging markets.

【References】

Cheng Y, Han L, Wu L, et al.
Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.
JAMA.
2022; 328(12):1223–1232.
doi:10.
1001/jama.
2022.
16464

*Image footage is from JAMA's official website

Contact details

Media: PR@Henlius.
com

Investor: IR@Henlius.
com

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