Another indication was approved, and serplulimab opened the first scene of harvest in the field of lung cancer

• Henlius has made a key breakthrough
in the field of small cell lung cancer around serplulimab to comprehensively cover the first-line treatment of lung cancer.

Serplulimab (Hansiform, H Drug) is Henlius' first innovative monoclonal antibody independently developed by Henlius, which was approved in China in March 2022 for the treatment of highly unstable microsatellite (MSI-H) solid tumors
.
Recently, the drug has been approved for a new indication - combined with carboplatin and albumin paclitaxel for the first-line treatment of inoperable resectable locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC), officially embarking on its new journey
in the field of lung cancer.

Lung cancer is one of the most common cancers in the world and has the highest incidence and mortality in China
.
Tumor immunotherapy, especially PD-1, PD-L1 antibodies have been recommended by Chinese and foreign guidelines for the treatment of negative driver genes EGFR, ALK and other negative and targeted drug resistance, and many related products at home and abroad are actively developing lung cancer indications
.

In addition to sqNSCLC, serplulimab is also exploring immunocombination therapy for indications such as non-squamous non-small cell lung cancer (nsqNSCLC) and limited-stage small cell lung cancer (LS-SCLC), forming a comprehensive layout
for first-line treatment of lung cancer.

Enrich treatment options in the field of non-small cell lung cancer

As a recombinant humanized anti-PD-1 monoclonal antibody injection, among the many PD-1 products that have been marketed at home and abroad, the differences of serplulimab are reflected in the
molecular design, clinical trial design and indication layout.

In terms of molecular design, first of all, serplulimab has undergone structural modification of S228P, which has the characteristics
of structural stability, antibody-dependent cytotoxic effect (ADCC), weak complement-dependent cytotoxic effect (CDC), and certain antibody-dependent cell phagocytosis (ADCP) effect.
In addition, serplulimab binds to the C'D ring and FG ring on the PD-1 molecule, and the binding epitope area is large, and its equilibrium dissociation constant value is small, and its affinity with the receptor is high, and the tumor suppressor activity is strong.
The production rate of anti-drug antibodies (ADA) is 2.
8%, and the immunogenicity is low
.

In terms of clinical trial design, for sqNSCLC, Henlius chose a combination of
serplulimab plus carboplatin and albumin paclitaxel.
From the clinical data of a number of PD-1/L1, this is the best matching regimen for combination chemotherapy at present, and has been authoritatively recommended
by NCCN, CSCO and other domestic and foreign guidelines.
The Phase III clinical study (ASTRUM-004), led by Professor Zhou Caicun of Shanghai Pulmonary Hospital, evaluated the efficacy and safety of serplulimab in combination with chemotherapy in the first-line treatment of patients with locally advanced or metastatic squamous non-small cell lung cancer, and the PFS and OS endpoints
were evaluated by an independent review committee.

In addition, Henlius has also prospectively laid out international multi-center research, opened research centers in China, Poland, Turkey and other countries, enrolled more than 500 patients worldwide, and included more than 30% of whites, becoming the only "Chinese" anti-PD-1 monoclonal antibody with sqNSCLC international clinical research data, which is also the "Chinese" PD-1 clinical study
with the largest sample size for sqNSCLC.
Its sufficient international clinical trial data is expected to lay the foundation for
global declaration and commercialization.

Advanced sqNSCLC is indicated for about 30% of advanced non-small cell lung cancer (NSCLC), and the approval of serplulimab will bring new treatment options
to this area.

In addition to sqNSCLC indications, Henlius has also conducted a phase III clinical study of serplulimab combined with Hambetal (bevacizumab) in the first-line treatment of advanced non-squamous non-small cell lung cancer (nsqNSCLC) in the field of non-small cell lung cancer, which is currently in the key research stage.
In addition, for squamous non-small cell lung cancer without driver genes, anti-PD-1 monoclonal antibody combined with chemotherapy is commonly used in clinical practice, and Henlius screened this population for high expression of EGFR, and then carried out phase II clinical trials of H drug combined with HLX07, which is expected to revolutionize the first-line treatment in
this field.

Fill the gap in PD-1 treatment of small cell lung cancer

Small cell lung cancer (SCLC) accounts for about 15%~20% of the total number of lung cancers and is the most aggressive subtype
of lung cancer.
Compared with non-small cell lung cancer, there are few drugs for small cell lung cancer, and the prognosis of patients is extremely poor
.
For the past 30 years, etoposide combined with cisplatin or carboplatin has been the first-line standard treatment for extensive-stage small cell lung cancer, and the advent of the immune era has brought a major breakthrough
in the treatment of small cell lung cancer.
A number of PD-1/PD-L1 products have been explored
in this indication.

In the IMpower133 study, the median overall survival (OS) of atezolizumab combined with carboplatin and etoposide was 12.
3 months (10.
3 months in the chemotherapy alone group).

In the CASPIAN study, median OS of duvalimab + etoposide + carboplatin or cisplatin was also better than that in the chemotherapy group (13 versus 10.
3 months), with a 27%
lower risk of death.
Based on this, these two PD-L1 products have been approved by the FDA and NMPA for first-line treatment
of ES-SCLC patients.
Both have also obtained the level I recommendation
of the CSCO Small Cell Lung Cancer Diagnosis and Treatment Guidelines for the first-line treatment of ES-SCLC.

But so far, no PD-1 has made a breakthrough
in the treatment of small cell lung cancer.
PD-1 inhibitor pioneers pembrolizumab and nivolumab have been explored in the first-line treatment of ES-SCLC, but they have failed to improve the patient's OS, so the corresponding indications
have been withdrawn.
Therefore, the performance of serplulimab in small cell lung cancer has attracted particular attention
from the industry.

According to data from the ASTRUM-005 study of serplulimab published in the Journal of the American Medical Association (JAMA), the median OS in the serplulimab and placebo groups was 15.
4 months (95% CI 13.
3–NE) and 10.
9 months (95% CI 10.
0–14.
3), with a hazard ratio (HR) of 0.
63 (95% CI 0.
49–0.
82; p<0.
001), respectively, The record median OS raises new heights in the potential
of PD-1 inhibitors in SCLC.

Further reading

The breakthrough results of domestic PD-1 inhibitor H drug have been listed in the international authoritative journal JAMA, overcoming many years of problems in the field of immunotherapy for small cell lung cancer

In April 2022, the Guidelines for the Diagnosis and Treatment of CSCO Small Cell Lung Cancer added a new regimen of serplulimab combined with EC as a level III recommendation
for the first-line treatment of ES-SCLC.
At present, the marketing registration application for this indication has been accepted by the NMPA in April 2022, and it is expected to become the first anti-PD-1 monoclonal antibody
for the first-line treatment of small cell lung cancer in China and even in the world.

In addition to the rapid completion of domestic registration applications, the global layout of serplulimab is also developing as planned: its indications for the treatment of small cell lung cancer have been granted orphan drug designation by the FDA in April 2022, and Henlius intends to submit the corresponding marketing application in the first half of 2024; Its international multicenter phase III study of combination chemotherapy concurrent radiotherapy in untreated LS-SCLC patients has also been approved for clinical study
through clinical trial registration by the Australian Medicines Administration (TGA).

Combination drugs and market potential