Platinum

FDA approved zolbetuximab-clzb for CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma, in combination with chemotherapy. Dr. Marshall highlights the need for CLDN18.2 testing and the potential benefits and manageable toxicities of zolbetuximab, emphasizing ongoing challenges in GI cancer treatment.

ODAC meeting concluded unfavorable risk-benefit profile of PD-1 inhibitors in PD-L1–negative gastrointestinal cancers, with ongoing debate on optimal use in patients with PD-L1 expression 1%-10%. Uboha suggests immunotherapy for PD-L1 CPS ≥1%, noting variability in expression and need for better treatments. Tislelizumab approval pending, with survival benefits seen in PD-L1 TAP ≥10% patients. ODAC discussed limiting approvals based on biomarker-selected populations due to lack of benefit in PD-L1–negative tumors.

Merck announces positive Phase 3 trial results for subcutaneous pembrolizumab with berahyaluronidase alfa in metastatic NSCLC, meeting primary pharmacokinetic endpoints and showing noninferiority compared to IV KEYTRUDA.

The FDA's approval of zolbetuximab-clzb in combination with chemotherapy for HER2-negative, CLDN 18.2-positive gastric or gastroesophageal junction adenocarcinoma marks a significant shift towards precision medicine in treating this cancer. The approval, supported by the SPOTLIGHT and GLOW trials, highlights the potential of targeting CLDN 18.2 to improve patient outcomes, encouraging further research and timely biomarker testing.

Zolbetuximab, a CLDN18.2-targeted IgG1 monoclonal antibody, combined with frontline chemotherapy, extended PFS and OS in HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma patients positive for CLDN18.2, according to phase 3 SPOTLIGHT and GLOW trials. The FDA approved zolbetuximab in October 2024 for first-line treatment of these patients. Median PFS was 9.2 months with zolbetuximab vs 8.2 months with placebo, and median OS was 16.4 months vs 13.7 months, respectively. Zolbetuximab was also approved in Japan and Europe in 2024.

The phase 3 KEYVIBE-008 trial found that co-formulated vibostolimab and pembrolizumab plus etoposide and platinum did not meet the primary end point of overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC) compared to atezolizumab plus EP. Median OS was 11.5 months vs 12.9 months, and median progression-free survival (PFS) was 5.3 months vs 4.5 months. The trial was discontinued due to the benefit/risk profile, though investigation continues in non–small cell lung cancer (NSCLC).

Astellas Pharma’s Vyloy (zolbetuximab-clzb) approved by FDA for first-line treatment of CLDN18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, in combination with chemotherapy. Supported by SPOTLIGHT and GLOW trials, Vyloy shows improved progression-free and overall survival. Now approved in US, EU, UK, Japan, and South Korea.

FDA approves Vyloy (zolbetuximab-clzb) with fluoropyrimidine- and platinum-based chemo for first-line treatment of locally advanced, unresectable or metastatic, HER2-negative gastric or gastroesophageal junction adenocarcinoma with CLDN18.2-positive tumors. Supported by phase 3 trials GLOW and SPOTLIGHT, Vyloy improved progression-free and overall survival. Common adverse events include nausea, vomiting, fatigue, and diarrhea. Vyloy is supplied as a 100 mg lyophilized powder for intravenous infusion.

Astellas Pharma secures FDA approval for Vyloy, a CLDN18.2-targeted therapy combined with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma. Vyloy is the first such therapy approved in the US, with Roche providing the companion diagnostic test. The approval is based on Phase 3 SPOTLIGHT and GLOW trials showing improved progression-free and overall survival.

The FDA approved Astellas Pharma Inc.’s VYLOY (zolbetuximab-clzb) for first-line treatment of CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction adenocarcinoma. VYLOY is the first CLDN18.2-targeted therapy in the U.S., approved based on Phase 3 SPOTLIGHT and GLOW trials showing improved progression-free and overall survival. Common side effects include nausea, vomiting, and decreased appetite.