The combination therapy of immunotherapy zolbetuximab and CAPOX (capecitabine + oxaliplatin) developed by Astellas is drawing attention by showing positive clinical results in Claudin (CLDN)18.2+ and HER2- progressive gastric and gastroesophageal junction (GEJ) adenocarcinoma.
On Tuesday (local time), the American Society for Clinical Oncology (ASCO) released the results of the GLOW study, the clinical trial of zolbetuximab, at its plenary series.
CLDN18.2 is a protein found in the gastric and gastroesophageal junction cells. Zolbetuximab has the mechanism to target CLDN18.2 and destroy cancer cells for the first time among anticancer drugs. However, no treatments have won approval to treat locally progressive resectable or metastatic gastric and gastroesophageal junction cancer with CLDN18.2 gene expression.
In the GLOW study, researchers randomly allocated 507 patients at a ratio of 1: 1 and administered CAPOX and placebo or CAPOX and zolbetuximab.
The participants were administered with CAPOX + placebo and CAPOX + zolbetuximab for eight cycles or more until they met disease progression or discontinuity standards.
The primary endpoint was the progression-free survival (PFS) of 13 months, and the secondary endpoint was overall survival (OS) during a maximum of 23 months of the follow-up period and objective response rate (ORR) during a maximum follow-up period of 13 months.
As a result, the median value of PFS (mPFS) of the zolbetuximab group was 8.2 months, and that of the placebo group was 6.8 months. The mOS were 14.4 months for the zolbetuximab group and 12.1 months for the placebo group.
Astellas said zolbetuximab induced positive results through the GLO(W study.
“The standard treatment for progressive gastric and gastroesophageal junction cancer in the United States is nivolumab (Opdivo) + fluoropyrimidine or platinum-based anticancer combination therapy,” said Dr. Pamela L. Kunz, a gastric cancer expert of ASCO. “In this study, zolbetuximab showed differences from nivolumab. Accordingly, it prolonged the survival of patients in CLDN18.2 + and HER2- progressive gastric and gastroesophageal cancer.”
Meanwhile, zolbetuximab also showed significant results in the clinical trial, which compared zolbetuximab + mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) and placebo + mFOLFOX6.
According to the SPOTLIGHT study results released at the ASCO’s gastrointestinal conference (ASCO GI 2023) in January, the primary endpoint of mPFS for the zolbetuximab group was 10.6 months, compared to the placebo group’s 8.7 months, reducing disease progression and death risks by 25 percent.
The secondary endpoint of mOS was 18.2 months for the zolbetuximab group, also lowering disease progression and death risks by 25 percent to the placebo group’s 15.5 months.
“The results of GLOW and SPOTLIGHT studies suggested the zolbetuximab + chemotherapy’s possibility as a new treatment option and standard treatment for CLDN18.2 + and HER2- locally progressive unresectable or metastatic gastric and gastroesophageal junction cancer patients,” said Dr. Rui-Hua Xu, professor of the Department of Medical Oncology at Sun Yat-Sen University Cancer Cancer.