NCT05078931

A Study to Evaluate Pembrolizumab Plus Lenvatinib in PD-L1 Positive TKI Resistant NSCLC Patients

An Open-label, Single-arm Phase II Study of Pembrolizumab Plus Lenvatinib in PD-L1 Positive Patients With TKI-resistant EGFR-mutated Advanced Non-small Cell Lung Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will investigate the efficacy and safety of the combination of pembrolizumab and lenvatinib in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC.

Detailed description

Tyrosine Kinase Inhibitors (TKIs) are the standard front-line treatment for patients with EGFR sensitive mutations. Even though patients have a better response rate and longer PFS comparing to chemotherapy, drug resistance have been an inevitable issue associated with these drugs. The standard of subsequent treatment for TKI resistance at present is chemotherapy (platinum doublet chemotherapy), which shows limited benefit with ORR 20-30% and PFS nearly 4 months. Therefore, it is essential to develop the novel therapies. Immune checkpoint therapy, which is based on negative regulatory mechanisms and targeted enhancement of the anti-tumor immune response, is a novel and important therapeutic strategy for lung cancer, especially for those patients with PD-1/PD-L1 positive advanced NSCLC. VEGF signaling regulates immune suppression by promoting the expansion of suppressive immune cell populations. Therefore, modulation of VEGF-mediated immune suppression could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors. Lenvatinib is a multitargeted TKI with anti-tumor activity via inhibiting VEGFR 1-3, FGFR 1-4 and PDGFR. It modulates the cancer immunity associated with a decrease in the population of immunosuppressive tumor-associated macrophages and an increase in interferon-γ-producing CD8+ T cells. The combination of immune check point inhibitors (PD-1/PD-L1 inhibitors) and lenvatinib could be a promising strategy to improve the immunotherapy outcome in lung cancer patients.

Conditions

• NSCLC

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200 mg will be administered as a 30-minute IV infusion every 3 weeks for up to 35 cycles
DRUG	Lenvatinib	Lenvatinib 20mg will be administered orally daily.

Timeline

• Start date: 2021-10-27
• Primary completion: 2025-12-30
• Completion: 2026-12-30
• First posted: 2021-10-15
• Last updated: 2025-07-30

Locations

1 site across 1 country: China