The FDA has granted priority review to the biologics license application for zolbetuximab as a treatment for patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.
The application for zolbetuximab has been granted priority review status for the frontline treatment of patients with CLDN18.2-positive locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.1
The FDA is expected to make a decision by January 12, 2024, under the terms of the Prescription Drug User Fee Act.
Two clinical trial results support the biologics license application (BLA)— the phase 3 SPOTLIGHT trial (NCT03504397) and GLOW (NCT03653507) trials.
Data from the SPOTLIGHT trial, which were presented during the 2023 Gastrointestinal Cancers Symposium, showed that frontline treatment with zolbetuximab, in addition to levofolinic acid, 5-Fluorouracil [5-FU] and oxaliplatin (mFOLFOX6), improved progression-free and overall survival (OS) compared with placebo plus mFOLFOX6, in patients with CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.2
The median progression-free survival (PFS) with the experimental combination was 10.61 months (95% CI, 8.90-12.48) vs 8.67 months (95% CI, 8.21-10.28) with the placebo-based regimen, yielding a 25% reduction in the risk of disease progression or death (HR, 0.751; 95% CI, 0.589-0.942; P = .0066).2
Further, the analysis demonstrated that the 12- and 24-month PFS rates in the experimental (n = 283) vs control groups (n = 282) were 49% and 24% with the novel agent, and 35% and 15% with placebo. All prespecified subgroups achieved a PFS benefit with zolbetuximab/mFOLFOX6, except for patients whose primary site of disease was GEJ (HR, 1.015; 95% CI, 0.649-1.586), or who were in the mixed/other Lauren classification of disease group (HR, 0.929; 95% CI, 0.601-1.434).2
The median OS with zolbetuximab/mFOLFOX6 vs placebo/mFOLFOX6, respectively, was 18.23 months (95% CI, 16.43-22.90) vs 15.54 months (95% CI, 13.47-16.53), for an HR of 0.75 (95% CI, 0.601-0.936; P = .0053).
Similarly, data from the GLOW trial, which were presented during the 2023 March ASCO Plenary Series, demonstrated that zolbetuximab, in addition to oxaliplatin plus capecitabine (CAPOX), also delivered a statistically significant improvement in PFS and OS compared with placebo plus CAPOX, in this patient population.3
The median follow-up times were 12.62 months for the zolbetuximab arm and 12.09 in the placebo arm, at which point, the median PFS was 8.21 months (95% CI, 7.46-8.84) vs 6.8 months (95% CI, 6.14-8.08), respectively (HR, 0.687; 95% CI, 0.544-0.866; P = .0007). The median OS between the 2 arms was 14.39 months (95% CI, 12.29-16.49) vs 12.16 months (95% CI, 10.28-13.67), respectively, (HR, 0.771; 95% CI, 0.615-0.965; P = .0118).3
“Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer. While rare in the United States, gastric cancer can be deadly when diagnosed in the late stages,” Moitreyee Chatterjee-Kishore, PhD, MBA, senior vice president and head of Immuno-Oncology Development at Astellas, stated in a news release.1 “The FDA’s acceptance of the BLA filing and priority review designation for zolbetuximab confirms the urgent therapeutic need and brings us one step closer to delivering on this commitment to patients, families, and caregivers.”