CStone Pharmaceuticals' registrational clinical study for the first-line treatment of esophageal squamous cell carcinoma has reached the primary endpoint and intends to submit a marketing application for ® a new indication

On January 3, 2023, CStone Pharmaceuticals (02616.
HK) reported that its potentially best-in-class PD-L1 antibody Zogeminec (sugemelimab ® injection) first-line clinical study for esophageal squamous cell carcinoma (GEMSTONE-304) reached the primary endpoint, and the combination of chemotherapy significantly ® improved progression-free survival (PFS) and overall survival (OS) in first-line treatment of patients with locally advanced, recurrent or metastatic esophageal squamous cell carcinoma that cannot be resected, with statistically significant and clinically
。 This is the fifth registrational clinical study
in which Zechem ® has achieved positive results.
Zegema became the world's first PD-L1 monoclonal antibody to achieve positive results for locally advanced, recurrent or metastatic esophageal squamous cell carcinoma ® that cannot be resected, while imported PD-L1 monoclonal antibodies including durvalumab and atezolizumab failed to achieve similar results
.

Dr.
Jianxin Yang, CEO of CStone Pharmaceuticals, said, "We are pleased to see the success
of Zegemin's ® research in esophageal cancer, a global cancer with high incidence.
This is also the fifth successful registration study after ® stage III and IV non-small cell lung cancer, extranodal NK/T-cell lymphoma, and gastric cancer, completing a grand slam achievement
in the treatment of high-incidence tumors.
Currently, no PD-L1 antibody has been approved for the treatment of esophageal cancer, and we look forward to promoting this new treatment to more patients
.
" As a biopharmaceutical company with the core of innovative research and development of tumor immunotherapy and precision therapy drugs, CStone will continue to focus on the research and development of first-in-class and best-in-class targets, and strive to bring more innovative therapies to patients
.
”

Recently, sugemalimab has also made significant progress in Europe, and its first marketing authorization application outside China, namely the first-line treatment of metastatic non-small cell lung cancer (NSCLC) with chemotherapy, was accepted
by the UK Medicines and Healthcare Goods Administration.
In 2021, sugemalimab received Innovative Licensing and Access Pathway (ILAP) qualification in the UK and is currently under accelerated review, and it is likely to become the first domestic PD-(L)1 monoclonal antibody
approved in Europe.

The GEMSTONE-304 study met its primary clinical endpoint

The GEMSTONE-304 study is a randomized, double-blind, multicenter, placebo-controlled, phase III registrational clinical trial designed to evaluate the efficacy and safety
of Gemstone-304 ® plus FP chemotherapy regimen (fluorouracil + cisplatin) as a first-line treatment for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma 。 The primary endpoints of the trial were PFS and OS assessed by the blinded Independent Centre Review Committee (BICR), and secondary endpoints included investigator-assessed PFS, BICR, and investigator-assessed objective response rate (ORR) and duration of response (DoR).

The phase Ib study presented at the 2020 ESMO Conference showed that the objective response rate of Jiema plus FP chemotherapy as the first-line treatment for advanced esophageal squamous cell carcinoma ® reached 67.
6% (25/37), the disease control rate reached 89.
2%, and the response was sustainable
.
The results of the GEMSTONE-304 study published this time showed that compared with placebo plus chemotherapy, the combination of chemotherapy ® significantly improved PFS and OS as assessed by the blinded Independent Center Review Committee (BICR), and the difference was statistically significant and clinically significant
.
The safety profile is consistent with the results of previously reported clinical studies related to Zejiemei, ® and no new safety signals
have been found.

Professor Li Jin, principal investigator of the GEMSTONE-304 study and director of the Department of Oncology, Dongfang Hospital Affiliated to Tongji University, said: "In clinical practice, about 70% of esophageal cancer patients have developed locally advanced or distant metastasis at the initial diagnosis of the disease, and even in operable esophageal cancer, 50%-60% of patients will relapse or develop distant metastasis
after surgery.
The success of the GEMSTONE-304 study shows that the combination of chemotherapy ® has shown good antitumor activity and good safety in the first-line treatment of esophageal squamous cell carcinoma
.
We expect this immunotherapy to provide new treatment options
for the majority of esophageal cancer patients.
" ”

Esophageal cancer has become one of the
most common cancers worldwide.
According to GLOBOCAN 2020 data, there were more than 600,000 new cases of esophageal cancer worldwide in 2020 (esophageal squamous cell carcinoma accounts for about 85%), and the number of deaths reached 544,000, making it the 8th most common cancer and 6th leading cause
of cancer death in the world.
Esophageal cancer is a malignant tumor with Chinese characteristics, and the incidence of esophageal cancer in China accounts for more than half of the world, and about 90% is esophageal squamous cell carcinoma
.

Zejiemei ® has created "the world's first" many times, highlighting the best potential in its class

Based on the results of this announcement, Zegemin ® became the world's first PD-L1 monoclonal antibody
to achieve positive results for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

In fact, Zegemin ® has been shown to outperform
other PD-L1 monoclonal antibodies in multiple clinical studies in a number of different indications.
In the field of stage IV NSCLC indications, Zegemin ® is the world's first combination chemotherapy approved first-line PD-L1 antibody for the treatment of patients with metastatic squamous and non-squamous NSCLC; In the field of stage III NSCLC indications, it is the world's first approved PD-(L)1 antibody for the treatment of patients with concurrent or sequential chemoradiotherapy stage III NSCLC; In the field of indications for gastric/gastroesophageal junction adenocarcinoma (GC/GEJ), it is the world's first PD-L1 monoclonal antibody to achieve positive results in GC/GEJ phase III clinical study, and OS shows a clear trend of benefit; In the field of relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL) indications, Zegema ® is expected to become the world's first tumor immunotherapy drug
approved for R/R ENKTL.

The outstanding efficacy advantage of Zejiemei ® compared with similar drugs is related to
the dual mechanism of action brought by its unique design.
First, it can block the binding of PD-L1 on the surface of tumor cells to PD-1 on the surface of T cells, relieve the inhibitory effect of PD-1/PD-L1 signaling pathway on T cells, activate specific immunity, and mediate T cell killing of tumors, which is also the common mechanism of action of all PD-L1 monoclonal antibodies; The second mechanism is unique to Zejiemei ®, which is its killer tool to achieve higher efficacy than other PD-L1, that is, it uniquely retains the structure with mediating activity when designed, which can activate innate immunity, mediate macrophages to further directly kill tumors, enhance antigen presentation, and stimulate the immune system to achieve long-term efficacy
.
® As a fully human, full-length anti-PD-L1 monoclonal antibody, it is the closest natural immunoglobulin 4 (IgG4) monoclonal antibody drug to the human body, with a lower
risk of immunogenicity and related toxicity in patients.

At present, Zejiemei ® has been approved by the National Medical Products Administration (NMPA) of China for phase IV and phase III NSCLC indications, becoming the world's first PD-(L)1 antibody covering both middle and advanced lung cancer indications, with wide safety and applicability; Its marketing application for the new indication for the treatment of R/R ENKTL has been accepted by the NMPA and included in the priority review; At the same time, CStone plans to submit to NMPA a marketing application
for two new indications for ® the treatment of GC/GEJ and esophageal squamous cell carcinoma.
CStone Pfizer, a strategic partner, has exclusive commercialization rights
in the ® Greater China market.