Drug intelligence / Profile preview

bevacizumab + binimetinib + pembrolizumab

Development stage
Phase 2
Lead developer
Merck
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

Bevacizumab + binimetinib + pembrolizumab is an investigational triplet combination therapy primarily studied for the treatment of microsatellite-stable (MSS), refractory metastatic colorectal cancer (mCRC). The regimen consists of three approved agents with distinct mechanisms: **pembrolizumab**, a PD-1 immune checkpoint inhibitor; **binimetinib**, a small molecule MEK 1/2 inhibitor; and **bevacizumab**, a VEGF-targeted monoclonal antibody. The rationale for this combination is based on the hypothesis that dual blockade of the MAPK and VEGF pathways can modulate the tumor immune microenvironment, potentially overcoming resistance to immunotherapy in typically "cold" MSS tumors. The combination was evaluated in a Phase II investigator-initiated trial (NCT03475004) conducted at the University of Colorado Comprehensive Cancer Center. While the study demonstrated a high disease control rate (70%) and acceptable tolerability in heavily pretreated patients, it did not meet its primary endpoint of significantly improving the objective response rate compared to historical controls.

Other names
pembrolizumab + binimetinib + bevacizumab
02

Targets

MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)PDCD1 (Programmed cell death protein 1 receptor)VEGFA (Vascular endothelial growth factor A)

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