Drug intelligence / Profile preview

cabozantinib + gefitinib + pembrolizumab

Development stage
Preclinical
Lead developer
Exelixis
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination therapy consisting of three agents: - **Cabozantinib** is a small molecule multi-tyrosine kinase inhibitor that targets several kinases including MET, VEGFR, and AXL. It inhibits tumor growth, angiogenesis, and metastatic progression. - **Gefitinib** is a small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks EGFR signaling pathways involved in cell proliferation and survival. - **Pembrolizumab** is a monoclonal antibody immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1), thereby enhancing T-cell mediated anti-tumor immune responses. This triple combination has not been reported in clinical trials or standard practice as of June 2025. While combinations of cabozantinib plus pembrolizumab have been studied for various cancers such as metastatic renal cell carcinoma (mRCC), gastroesophageal adenocarcinoma (mGEA), and urothelial carcinoma[1][2][3][4][5][6], there are no published studies or clinical data on the use of all three agents—cabozantinib, gefitinib, and pembrolizumab—together. Each drug has distinct mechanisms targeting both tumor-intrinsic pathways (kinase inhibition) and the immune microenvironment (checkpoint blockade).

02

Targets

AXL (AXL receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)PDCD1 (Programmed cell death protein 1 receptor)EGFR T790M (Epidermal growth factor receptor T790M mutant)VEGFR2 (Vascular endothelial growth factor receptor 2)

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