Professor Zhou Caicun talks about the key study of serplulimab being approved for lung squamous cell carcinoma indications

Heavy! Serplulimab ranks among the first-line treatments for lung squamous cell carcinoma!

Based on the excellent efficacy and safety shown in ASTRUM-004 study, on November 1, the original Chinese drug serplulimab combined with albumin paclitaxel and carboplatin was approved by the National Medical Products Administration of China (NMPA) for the first-line treatment
of locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC).
。 Since then, serplulimab has entered the field of advanced NSCLC drug treatment, bringing a new first-line treatment option for lung squamous cell carcinoma patients, and also demonstrating the world-class research strength
of China's clinical research.
On this occasion, the "medical community" specially invited Professor Zhou Caicun of Shanghai Pulmonary Hospital affiliated to Tongji University to deeply analyze the ASTRUM-004 research and the new pattern
of NSCLC diagnosis and treatment in China.

Serplulimab entered the field of tumor treatment, and good news was frequent

In March 2022, serplulimab was approved by the NMPA for the treatment of unresectable or metastatic microsatellite highly unstable (MSI-H) solid tumors; The 2022 Guidelines for the Diagnosis and Treatment of Small Cell Lung Cancer of the Chinese Society of Clinical Oncology (CSCO) recommend serplulimab for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) based on Class 1A evidence; Just recently, serplulimab was once again approved for first-line treatment
of lung squamous cell carcinoma.
The indications for the treatment of serplulimab have been further expanded, and its anti-tumor activity has been demonstrated across multiple tumor species, which is expected to benefit more patients with
malignant tumors.

At the beginning of 2022, serplulimab took the lead in the field of MSI-H solid tumor treatment, and at the annual meeting of the American Society of Clinical Oncology (ASCO) that year, it announced the latest data
of its key study approved for its indication (ASTRUM-010 study).
。 The results showed that the objective response rate (ORR) of 68 patients in the main efficacy analysis population (MEAP) was 39.
7% (95% CI: 28.
0%-52.
3%), and the ORR of 58 patients in the sensitive efficacy analysis population (SAP) was as high as 43.
1% (95% CI: 30.
2%-56.
8%).
The 12-month survival (OS) rate in MEAP and 82.
4%
in SAP was 74.
5%.
In terms of safety, only 13 patients (12.
0%) had grade ≥ immune-related adverse events, and the overall safety profile ^{was good [1].}

The results showed that serplulimab had significant antitumor activity and good safety
in patients with unresectable or metastatic MSI-H/mismatch repair gene defect (dMMR) solid tumors.

In the field of ES-SCLC therapy, serplulimab combined with chemotherapy has achieved breakthrough results
.
The ASTRUM-005 study explored the efficacy and safety
of serplulimab in combination with chemotherapy for the first-line treatment of ES-SCLC 。 The median OS (mOS) in the experimental group was as high as 15.
4 months (HR=0.
63, 95CI%: 0.
49-0.
82, P<0.
001), and the 2-year OS rate was 41.
3%, which was more than 30% compared with the placebo group; Median progression-free survival (mPFS) was also significantly better than placebo (5.
8 versus 4.
3 months, HR=0.
47, 95% CI: 0.
38–0.
59, P < 0.
001); The ORR reached 80.
2%, and most patients achieved deep tumor remission^[2].

As the world's first study with positive results in the first-line treatment of ES-SCLC with programmed death receptor 1 (PD-1) inhibitors, ASTRUM-005 was presented at the 2022 ASCO Conference in the form of an oral report and was listed in JAMA, the top international medical journal, marking the international recognition
of China's original drug.

Figure 1.
ASTRUM-005 study honored JAMA

Just recently, even more exciting news, serplulimab "next city", combined with albumin paclitaxel and carboplatin, has been approved by the NMPA for the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma.

This means that serplulimab has become the only original PD-1 inhibitor
in China that has achieved positive results in both ES-SCLC and sqNSCLC registration studies.

A new breakthrough has been made in the treatment of lung squamous cell carcinoma, and serplulimab has brought a new first-line treatment option to patients with lung squamous cell carcinoma

Compared with lung adenocarcinoma, lung squamous cell carcinoma has a higher frequency of somatic mutations and stronger immunogenicity, which is theoretically more suitable for immunotherapy
.
Up to now, a number of studies have proved that immunocombination therapy can bring greater survival benefits to patients with lung squamous cell carcinoma ^[3-6], and a number of immunotherapy drugs have been approved for lung squamous cell carcinoma
.
Therefore, in real-world clinical practice, there are more diverse options for first-line treatment of lung squamous cell carcinoma
.
The approval of serplulimab as a first-line treatment for lung squamous cell carcinoma is undoubtedly a problem
that clinicians need to think about in the face of diverse treatment "weapons" How clinicians choose "standardized" and "personalized" diagnosis and treatment strategies for patients.

A phase III ASTRUM-004 study led by Professor Zhou Caicun provides new ideas
for the clinical diagnosis and treatment of lung squamous cell carcinoma in China with a research design and breakthrough efficacy and safety data that are more in line with China's clinical practice.

The study design is "rigorous" and "high-quality", which is more in line with Chinese clinical practice

"The ASTRUM-004 study is a global multicenter, randomized, double-blind Phase III clinical study conducted against international standards, with a randomized, double-blind design and evaluation by an Independent Regulatory Review Board (IRRC) in accordance with RECIST 1.
1 to make the data more objective
.
The chemotherapy regimen of albumin paclitaxel + carboplatin is also a more widely used combination chemotherapy regimen
for clinical lung squamous cell carcinoma patients in China.
At the same time, the control group also used this chemotherapy regimen to make the data closer to China's clinical practice and bring more scientific guidance
to China's clinical practice.
”

PFS benefits are significant, PFS extension is better, and OS has a trend of benefit

In this pivotal study of first-line immunotherapy for lung squamous cell carcinoma, serplulimab showed excellent mPFS in the Chinese group for 9.
79 months, and was more than 4 months higher than that in the control group (9.
79 months vs 5.
72 months, HR=0.
44, 95% CI: 0.
32-0.
59).

This suggests that patients with first-line treatment with serplulimab plus chemotherapy will have a more significant survival benefit
than chemotherapy.

In addition, it is the OS
that is even more noteworthy.
Professor Zhou Caicun said that the study had clearly observed the trend of OS benefit (HR=0.
60, 95% CI: 0.
39-0.
92)
in combination with immunochemotherapy.
As Professor Zhou Caicun said, the "long tailing" effect of immunotherapy is more reflected
in OS data.
It is expected that the combination of serplulimab + chemotherapy will bring more significant survival benefits
to patients with lung squam cell carcinoma.

The ORR is 75% and the DoR is 10.
6 months

The emergence of new treatment options is accompanied by the expectation of achieving tumor remission
for more patients.
Professor Zhou Caicun interpreted the relevant data in detail in the study, he said that the ORR of the serplulimab + chemotherapy combination therapy group in the Chinese group was as high as 75%, which was about 20% higher than that of the control group, and the addition of serplulimab achieved tumor remission
for more patients.
In addition, the duration of response (DoR) in the experimental group was 10.
6 months, which was half a year longer than that of the control group, indicating that more patients could benefit significantly
.

Another major advantage of immunotherapy is that it is more controllable than chemotherapy, and the ASTRUM-004 study has a similar safety profile to similar studies, no new adverse events have been found, and the overall safety profile is good and tolerated
by patients.

The application prospect of serplulimab is broad

When talking about the impact of serplulimab combination therapy on the diagnosis and treatment pattern of lung cancer, Professor Zhou Caicun said that immunotherapy has made great progress in the field of lung squamous cell carcinoma in recent years, and has become an important treatment method for lung squamous cell carcinoma, and serplulimab has become the only original PD-1 inhibitor in China that has obtained positive results in the first-line registration clinical study of SCLC and NSCLC, which has great potential and will bring longer survival benefits
to lung cancer patients 。 However, at the same time, it should still be noted that the diagnosis and treatment of lung cancer still faces many difficulties, especially advanced lung cancer still seriously affects people's lives and quality of life, and the relevant exploration of lung squamous cell carcinoma treatment will continue
.
The approval of serplulimab for lung squamous cell carcinoma is a milestone, and it is expected that Chinese doctors will use more Chinese original drugs, accumulate drug experience, and continue to explore
in the direction of combination therapy, sequential therapy and the advancement of immune drug indications.

At present, serplulimab has been orphan drug designation by the US Food and Drug Administration (FDA), ASTRUM-005 study has been honored in JAMA, ASTRUM-004 study has been carried out in multiple centers around the world, and serplulimab has started head-to-head comparison of atezolizumab small lung research in the United States, which is expected to go to Europe and the United States, all indicating that the quality of serplulimab has been internationally recognized, and China's original drug has gone abroad and entered the international stage, looking forward to serplulimab being approved for indications abroad.
Bringing good news
to lung cancer patients around the world.