Express significantly improves progression-free survival of advanced gastric cancer! Potential "first-in-class" therapies show impressive Phase 3 clinical data

Today, Astellas Pharma announced that zolbetuximab, an investigational antibody therapy targeting Claudin18.
2 (CLDN18.
2), in combination with chemotherapy, has met its primary endpoint in a Phase 3 clinical trial for the first-line treatment of patients with locally advanced unresectable or metastatic gastric cancer and gastroesophageal junction (GEJ) adenocarcinoma, significantly prolonging progression-free survival (PFS).

These patients had tumors
positive for CLDN18.
2 and negative for HER2.
This is Astellas' second Phase 3 trial positive data
on zolbetuximab in the treatment of gastric cancer patients in a month.

Stomach cancer is the fifth most commonly diagnosed cancer and the fourth leading cause
of cancer death worldwide.
In 2020, there were nearly 1.
1 million newly diagnosed stomach cancer cases worldwide, resulting in 768,000 deaths
.
More than 70% of stomach cancer patients are diagnosed at an advanced stage, and the 5-year survival rate of these patients is only about 6%, and they are in urgent need of innovative therapies
.
Claudin (CLDN) is an important protein in the tight junction of normal tissues, with 4 transmembrane domains, which are involved in the regulation
of processes such as paracellular permeability and conductance.
CLDN18.
2 is highly expressed
in cancers of the digestive tract, including gastric cancer.
Therefore, CLDN18.
2 has the potential to become an effective target for the treatment of
solid tumors such as gastric cancer and pancreatic cancer.
There are still no therapies approved to target CLDN18.
2
.

Zolbetuximab is a potential "first-in-class" IgG1 monoclonal antibody that binds specifically to CLDN18.
2 on the surface of tumor cells, leading to cancer cell death
by initiating antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Image source: 123RF

The announced GLOW trial is a global, multicenter, double-blind Phase 3 clinical trial with a total of 507 patients enrolled to examine the efficacy and safety
of zolbetuximab in combination with placebo and CAPOX chemotherapy regimens as first-line therapy in patients with locally advanced unresectable or metastatic gastric cancer and GEJ adenocarcinoma.
Data analysis showed that the GLOW trial met the primary endpoint that zolbetuximab combination therapy statistically significantly improved PFS
compared with placebo combination therapy.
In addition, zolbetuximab combination therapy statistically significantly improved overall survival (OS), a key secondary endpoint
of the trial.
The most common associated adverse effects of treatment (TEAE) include nausea and vomiting
.

"We are excited
to share the top-line positive data from the SPOTLIGHT trial again after sharing the positive data from the SPOTLIGHT trial last month 。 This once again validates the potential of zolbetuximab as a potential gastric cancer therapy and an important milestone in our gastric cancer development program," said Dr.
Ahsan Arozullah, Head of Therapeutics Therapy Development and Senior Vice President of Astellas, "We will discuss these results with regulators and continue to promote the development of zolbetuximab as a first-line therapy for patients with locally advanced unresectable or metastatic gastric cancer and GEJ adenocarcinoma
。 ”