It's time for China to innovate! Professor Cheng Ying and ASTRUM-005 research were listed in international authoritative journals, refreshing the survival height of SCLC

On September 27, 2022, Beijing time, JAMA (Journal of the American Medical Association, impact factor 157.
335), one of the four top medical journals, published the full text online by Cheng Ying of Jilin Cancer Hospital Results of ASTRUM-005 (NCT04063163)1 in the global multicenter phase III clinical study of serplulimab (HLX10) in combination with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC)
led by the professor.

The results of the study showed that the median overall survival (OS) of serplulimab combined with chemotherapy first-line was 15.
4 months, reaching an unprecedented survival height
.
The inclusion of ASTRUM-005 in JAMA is a breakthrough for the change of ES-SCLC treatment pattern
.
It is worth mentioning that this is the ASTRUM-005 research after being featured in the oral report of the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting once again on the international academic stage, which shows that the gold content of the study and its important value to the SCLC field in China and even the world, it is the beginning of Chinese researchers leading SCLC immunotherapy to a better way, and it is also a microcosm of the rapid development of China's innovative pharmaceutical companies!

Beyond endlessly! The median OS was 15.
4 months, and the OS HR was 0.
63, exploring a new height of ES-SCLC survival

Treatment of SCLC has been slow to develop over the past 30 years, with platinum-based drugs plus etoposide chemotherapy regimens dominating
.
The development of immunotherapy has brought about a turnaround in lung cancer treatment, but unlike non-small cell lung cancer (NSCLC), immunotherapy has made few advances in the field of SCLC
.
Previous research data suggest that PD-L1 inhibitors can only prolong the survival of patients with ES-SCLC by about 2 months, while PD-1 inhibitors have mostly failed in the exploration of first-line treatment of ES-SCLC2-5
.
Therefore, improving overall survival of ES-SCLC remains the most urgent clinical unmet need
.

The ASTRUM-005 study is the first international multicenter clinical study led by Chinese investigators to conduct the largest PD-1 inhibitor for ES-SCLC indications, aiming to compare the efficacy and safety
of serplulimab and placebo in the first-line treatment of ES-SCLC with standard chemotherapy (EC regimen: carboplatin + etoposide), respectively.
A total of 585 patients were included in the study, of which 400 (68.
4%) were Chinese patients
.
The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, and immunogenicity
.

The results showed that serplulimab combined with chemotherapy significantly prolonged the patient's OS, becoming the first PD-1 inhibitor
in the world to achieve a positive result in first-line treatment of ES-SCLC 。 The median OS of the serplulimab group was 15.
4 months, which was 4.
5 months longer than that of the control group of 10.
9 months, with an HR of 0.
63 (95% CI 0.
49-0.
82; P < 0.
001), and a significant reduction in the risk of death by 37%, which is the longest clinical study in all first-line immunological ES-SCLC studies, and the OS HR value also stands out
among other similar studies 。 In addition, the 2-year OS rate of 43.
1% in the serplulimab group and only 7.
9% in the control group meant that more than two-fifths of patients could survive for more than 2 years
with serplulimab regimen.

Figure OS analysis

Reap the benefits across the board! Multiple positive results of PFS, ORR, and DOR show China's strength and lead the global breakthrough

In addition to the primary endpoint OS, serplulimab also brings the full range of PFS, ORR, and OR benefits
.
The median PFS was 5.
7 months versus 4.
3 months, PFS HR 0.
48, and the risk of disease progression or death was reduced by 52%.

PFS HR in previous studies of the same type was around 0.
80, and PFS HR in ASTRUM-005 achieved a breakthrough of less than 0.
50, suggesting that serplulimab also has unique advantages
in delaying disease progression.
In addition, the 12-month PFS rates of the two groups were 23.
8% and 6.
0%, respectively, and the PFS curves showed early separation and persisted
at about 2 months.

Figure PFS analysis

The ORR of the serplulimab group reached 80.
2%, which was nearly 10%
higher than that of the control group.
Compared with the ORR of 60%~70% of the same type of research, serplulimab treatment has made a large breakthrough, suggesting that a wider population can benefit from it2,3
.
The 6-month and 12-month DOR rates in the serplulimab group were significantly better than those in the control group (45.
1% vs 17.
1%, 24.
0% vs 8.
9%), and the median DOR of the two groups was 5.
6 months vs 3.
2 months, respectively, demonstrating the persistent antitumor activity
of serplulimab.

Table Mitigation Analysis

Safe and co-escorted! With controllable peace of mind, serplulimab is expected to redefine the new standard of ES-SCLC immunotherapy

The safety profile of serplulimab was controllable, with similar rates of adverse events (AEs) in the two groups, with 82.
5% versus 80.
1% of TEAEs occurring during the ≥ 3rd grade treatment period, 33.
2% vs 27.
6% of the TRAEs associated with serplulimab/placebo in ≥grade 3, and 4.
9% vs 4.
1% of TRAEs leading to discontinuation and 0.
8% vs 0.
5% of deaths related to study drugs, respectively , there was no difference
between the two groups.

Table Adverse Event Analysis

JAMA is the top journal in the global medical field, with the improvement of the research level of Chinese researchers, the development of independent innovative drugs in China, in recent years, China's original research has also begun to win JAMA, but in the field of SCLC immunotherapy This is the first research favored by JAMA, the level and clinical significance of this research has been affirmed by international peers, PD-1 inhibitor serplulimab will release great potential
in the clinical application of ES-SCLC in China and even the world 。 Domestic innovative drugs continue to speak out on the international stage, injecting new blood into the global progress of new drugs, bringing new breakthroughs, and demonstrating national self-confidence and strength
.