NCT07149090

Lenvatinib in Combination With Nivolumab Plus Chemotherapy in Metastatic Gastric Cancer Patients With Malignant Ascites

A Clinical Trial Evaluating the Efficacy and Safety of Lenvatinib, Nivolumab, and Chemotherapy in Metastatic Gastric Cancer With Malignant Ascites.

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 61 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

To investigate efficacy and safety of lenvatinib in combination with nivolumab plus chemotherapy in gastric cancer patients with peritoneal metastasis and grade ≥ 2 ascites.

Detailed description

Gastric cancer is the 4th leading cause of cancer-related mortality and the 5th most common malignancy worldwide. The past decade has seen significant progress in first-line systemic chemotherapy for patients with advanced gastric cancer. Immune checkpoint inhibitor (ICI)-based chemotherapy has become the standard first-line treatment since the demonstration of improved overall survival (OS) due to nivolumab plus chemotherapy in the Checkmate-649 study. Subsequent phase 3 trials have also demonstrated the positive impact of adding ICI to chemotherapy on survival. However, a proportion of patients still show poor survival outcomes with first-line ICI plus chemotherapy, highlighting an unmet need to improve treatment outcomes in such patients. While patients with microsatellite instability (MSI)-high gastrointestinal cancers exhibit favorable outcomes with ICIs, MSI-high gastrointestinal cancers with peritoneal metastases and ascites exhibited highly unfavorable outcomes to ICI-based therapies. To this end, a research team analyzed the survival outcomes of gastric cancer patients treated with first-line nivolumab plus chemotherapy, finding that patients with peritoneal metastasis and grade ≥ 2 ascites had detrimental survival outcomes despite a high PD-L1 CPS (≥5). Ascites VEGF level was reportedly high in patients with a large amount of malignant ascites, supporting the concept that anti-VEGF therapies are promising for treating gastric cancer patients with peritoneal metastasis. Lenvatinib is a potent multiple RTKi that selectively inhibits VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), VEGFR3 (FLT4), FGFR1-4, PDGFRα, c-KIT, and RET, which is approved for use in various cancer types, including hepatocellular carcinoma. Among known kinase inhibitors in clinical use, lenvatinib is one of the only inhibitors currently labeled with a mechanism of action as an inhibitor of not only VEGFRs but also FGFRs, both of which are currently believed to be very important for tumor angiogenesis. It is hypothesized that the addition of lenvatinib to nivolumab plus chemotherapy in gastric cancer patients with peritoneal metastasis and grade ≥ 2 ascites could improve survival outcomes for these patients. A prospective phase Ib/II trial has been designed to investigate the efficacy and safety of lenvatinib in combination with nivolumab plus chemotherapy in gastric cancer patients with peritoneal metastasis and grade ≥ 2 ascites.

Conditions

• STOMACH NEOPLASM
• Gastric Cancer
• Gastric Cancer Adenocarcinoma Metastatic

Interventions

Type	Name	Description
DRUG	Lenvatinib	Description: Lenvatinib: 12 mg (for body weight ≥ 60 kg) or 8 mg (for body weight \< 60 kg) per oral once daily * Dose level 1: 8mg per oral once daily (for \<60kg) 12mg per oral once daily (for ≥ 60kg) * Dose level 2: 4mg per oral once daily (for \<60kg) 8mg per oral once daily (for ≥ 60kg) Nivolumab: 360 mg administered intravenously every 3 weeks Chemotherapy(Oxaliplatin+Capecitabine) every 3 weeks * Capecitabine 1000 mg/m² per oral twice daily on Days 1-14 * Oxaliplatin 130 mg/m² administered intravenously on Day 1

Timeline

• Start date: 2025-11-11
• Primary completion: 2027-07-30
• Completion: 2027-07-30
• First posted: 2025-08-29
• Last updated: 2025-11-20

Locations

1 site across 1 country: South Korea