Astellas Pharma Inc. will present detailed results from the Phase 3 SPOTLIGHT trial evaluating first-line treatment with zolbetuximab, an investigational first-in-class Claudin 18.2 (CLDN18.2) targeted monoclonal antibody, plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. In the study, investigational treatment zolbetuximab plus mFOLFOX6 demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to placebo plus mFOLFOX6. Specifically, zolbetuximab plus mFOLFOX6 reduced the risk of progression or death by 24.9% (n=565; Hazard Ratio [HR]=0.751; [95% Confidence Interval [CI]: (0.598-0.942)]; P=0.0066) compared to placebo plus mFOLFOX6, meeting SPOTLIGHT's primary endpoint.

Median PFS was 10.61 months (95% CI: 8.90-12.48) in the treatment arm and 8.67 months (95% CI: 8.21-10.28) in the placebo arm. The study also showed that zolbetuximab plus mFOLFOX6 significantly prolonged OS, reducing the risk of death by 25.0% (HR=0.750; 95% CI: 0.601-0.936; P=0.0053). Median OS was 18.23 months (95% CI: 16.43-22.90) and 15.54 months (95% CI: 13.47-16.53) for the treatment arm and placebo arm, respectively.

The incidence of serious treatment-emergent adverse events (TEAEs) was similar between both arms (44.8% versus 43.5% in the zolbetuximab versus placebo arms) and consistent with previous studies. The most frequent TEAEs in the SPOTLIGHT study were nausea (82.4% versus 60.8%), vomiting (67.4% versus 35.6%) and decreased appetite (47.0% versus 33.5%). These new data from the SPOTLIGHT trial will be presented at the 2023 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in an oral presentation (Abstract LBA292; January 19, 1:30 p.m. PT) by Kohei Shitara, MD, Primary Investigator for SPOTLIGHT Study and Chief, Department of Gastrointestinal Oncology, the National Cancer Center Hospital East in Kashiwa, Japan.

SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (combination regimen of oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment of patients with CLDN18.2-positive, HER2- negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. The study enrolled 565 patients at 220 study locations in the U.S., United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival of participants treated with combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6.

Secondary endpoints include overall survival, objective response rate, duration of response, safety and tolerability and quality-of-life parameters. GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus CAPOX (a combination chemotherapy regimen which includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment of patients with CLDN18.2 positive, HER2- negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. The study enrolled 507 patients at 165 study locations in the U.S., Canada, United Kingdom, Europe, South America and Asia.

The primary endpoint is progression-free survival of participants treated with combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include overall survival, objective response rate, duration of response, safety and tolerability and quality-of-life parameters.