On March 15, 2024 CStone Pharmaceuticals (HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported that the China National Medical Products Administration (NMPA) has approved its new marketing application for Zygenix ( sugemalimab injection) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma expressing PD-L1 (combined positive score [CPS] ≥5) (Press release, CStone Pharmaceauticals, MAR 15, 2024, View Source [SID1234656251]). Zygenix becomes the world’s first PD-L1 monoclonal antibody approved for this indication.
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Dr. Jianxin Yang, CEO of CStone Pharmaceuticals, said, "We are very pleased that Zegemet has been approved in combination with chemotherapy for the first-line treatment of gastric cancer patients in China. This further demonstrates the clinical value and potential of Zegemet . Zegemet has previously been approved in China for indications including stage III and IV non-small cell lung cancer, extranodal NK/T-cell lymphoma, and esophageal squamous cell carcinoma. With this, Zegemet has achieved a grand slam achievement of approval for all five target indications. We are currently in discussions with the U.S. Food and Drug Administration (FDA) regarding registration and marketing approval in the U.S., and will continue to communicate closely with global regulatory agencies such as the European Medicines Agency (EMA) to further advance Zegemet ‘s global registration and marketing. We look forward to Zegemet benefiting more cancer patients worldwide."
Professor Lin Shen from Peking University Cancer Hospital, Principal Investigator of the GEMSTONE -303 study of Zygen, said: "China is one of the countries with the heaviest burden of gastric cancer globally. Clinically, most gastric adenocarcinoma patients are already in the advanced stage at the time of initial diagnosis and cannot undergo surgical resection. The prognosis for patients with advanced or metastatic gastric cancer is generally poor, and there is a huge unmet medical need. Zygen is the first approved PD-L1 monoclonal antibody with a clear biomarker for gastric cancer, and will undoubtedly provide more options for the precision treatment of G/GEJ patients. We hope that Zygen can be put into clinical use as soon as possible, bringing new hope for treatment to more gastric cancer patients."
The approval of the new marketing application for Zegnimet for gastric cancer is based on the GEMSTONE-303 study, a multicenter, randomized, double-blind, placebo-controlled Phase III registration clinical trial designed to evaluate the efficacy and safety of Zegnimet in combination with oxaliplatin and capecitabine as a first-line treatment for patients with locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma whose tumors are unable to undergo surgical resection and whose PD-L1 expression is ≥5%. The primary endpoints of the trial are PFS and OS assessed by the investigator, and secondary endpoints include PFS assessed by a blinded independent central review committee (BICR) and objective response rate (ORR) and duration of response (DoR) assessed by the investigator. The study has achieved its pre-specified dual primary endpoints.
Previously, the results of the Phase III GEMSTONE-303 study of Zegma combined with chemotherapy as the first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma were selected as a late- breaking abstract (LBA) at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, and detailed data were announced in the form of an oral report.
The data presented at the 2023 ESMO (Free ESMO Whitepaper) Congress were based on the final analysis of PFS, with a cutoff date of August 6, 2022, and the final analysis of OS, with a cutoff date of July 9, 2023. The results showed that the GEMSTONE-303 study met its pre-specified co-primary endpoints. In patients with PD-L1 expression ≥5%, Zegma combined with chemotherapy significantly improved PFS and OS compared to placebo combined with chemotherapy , with the differences being statistically significant and clinically meaningful.
The key results are as follows:
The median PFS assessed by investigators in the Zegemet treatment group and the placebo group was 7.6 months vs. 6.1 months, with a hazard ratio (HR) of 0.66 (95% CI, 0.54-0.81), P<0.0001 .
The OS of the Zegemet treatment group and the placebo group was 15.6 months vs 12.6 months, with a hazard ratio (HR) of 0.75 (95% CI, 0.61-0.92), P=0.0060 .
Subgroup analysis showed that all pre-set subgroups, including PD-L1 expression status, showed clinical benefits.
The investigator-assessed ORR for the Zegemet treatment group and the placebo group was 68.6% vs 52.7%, and the median DoR was 6.9 months vs 4.6 months .
Zegemet combined with chemotherapy has good tolerability and safety, and no new safety risks have been found .
About Gastric Cancer
Gastric cancer is one of the most common cancers worldwide. According to GLOBOCAN 2020 data, there were over 1 million new cases of gastric cancer and 769,000 deaths worldwide in 2020, making it the fifth most common cancer and the fourth leading cause of cancer death. China is one of the countries with the heaviest burden of gastric cancer, accounting for nearly half of the global number of new cases and deaths each year. Gastric adenocarcinoma accounts for over 90% of gastric malignancies, and the incidence of gastroesophageal junction adenocarcinoma has also been increasing in recent years.
About Zegemet ( sugemalimab injection)
Zegemet is an anti-PD-L1 monoclonal antibody developed by CStone Pharmaceuticals. Its development is based on the OmniRat transgenic animal platform, licensed from US-based Ligand Corporation . This platform enables the one-stop production of fully human antibodies. As a fully human, full-length anti-PD-L1 monoclonal antibody, Zegemet is the closest to the natural G-type immunoglobulin 4 (IgG4) response in the human body. Zegemet offers a lower risk of immunogenicity and related toxicities in patients, giving it a distinct advantage over similar drugs.
Currently, China’s NMPA has approved five indications for Zegemet :
First-line treatment in combination with chemotherapy for patients with metastatic squamous and non-squamous non-small cell lung cancer (NSCLC);
For the treatment of patients with unresectable, stage III non-small cell lung cancer who have not experienced disease progression after concurrent or sequential chemoradiotherapy;
Treatment of patients with relapsed or refractory extranodal NK/T-cell lymphoma;
First-line treatment in combination with fluoropyrimidine and platinum chemotherapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma; and
In combination with fluorouracil-containing and platinum-based chemotherapy, it is used for the first-line treatment of unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma that expresses PD-L1 (combined positive score [CPS] ≥ 5).
In addition, both the European Medicines Agency (EMA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have accepted marketing authorization applications for sugemalimab combined with chemotherapy for the first-line treatment of metastatic NSCLC. Both applications are currently under review.
CStone Pharmaceuticals and Pfizer have reached a strategic collaboration, including a strategic collaboration between CStone Pharmaceuticals and Pfizer Investment on the development and commercialization of Zegemet in mainland China, and a collaboration framework between CStone Pharmaceuticals and Pfizer Investment to introduce more oncology products into Greater China.