Table 2

Clinical trials of agents depleting TAMs or preventing their recruitment

Target	Agent	Mechanism of action	Combination partners	Phase	Status	Results	Identifier	Ref.
CSF1R	Emactuzumab	antagonistic anti-CSF1R mAb	Monotherapy; paclitaxel	I	Completed	↓immunosuppressive TAMs; no clinically relevant antitumor activity	NCT01494688	115
			Paclitaxel+anti-VEGF-A mAb bevacizumab	II	Active	–	NCT02923739	–
			Agonistic anti-CD40 mAb selicrelumab	I	Completed	↓CD14^dimCD16^bright monocytes; ↑activated Ki67⁺CD8⁺T cells; limited objective clinical responses	NCT02760797	116
	Cabiralizumab	Antagonistic anti-CSF1R mAb	Anti-PD-1 mAb nivolumab	I	Completed	–	NCT02526017	–
	LY3022855	Antagonistic anti-CSF1R mAb	Anti-PD-L1 mAb durvalumab; anti-CTLA-4 mAb tremelimumab	I	Completed	Limited clinical activity	NCT02718911	117
	Pexidartinib	Inhibitor of CSF1R tyrosine kinase activity	Paclitaxel	I	Completed	–	NCT01525602	–
	(PLX3397)
			Pembrolizumab	I/II	Terminated	Insufficient evidence of clinical efficacy	NCT02452424	–
CCL2	Carlumab (CNTO888)	Anti-CCL2 mAb neutralizing CCL2-induced chemotaxis	Monotherapy	I	Completed	Evidence of antitumor activity	NCT00537368	123
CCL2			SoC chemotherapy	I	Completed	Limited tumor responses	NCT01204996	122
Ang2	MEDI3617	Anti-Ang2 mAb inhibiting Ang2 binding to TIE2	Monotherapy; paclitaxel; paclitaxel+carboplatin; bevacizumab	I	Completed	Limited clinical activity	NCT01248949	124
	Trebananib (AMG-386)	Anti-Ang peptibody inhibiting Ang1/2 binding to TIE2	Paclitaxel+carboplatin	III	Terminated	No improvement in PFS	NCT01493505	125
			Pembrolizumab	I	Active	–	NCT03239145	–
VEGF/ Ang2	Vanucizumab (RG7221)	Anti-VEGF/Ang2 bispecific mAb inhibiting neoangiogenesis	Monotherapy; anti-PD-L1 mAb atezolizumab	I	Completed	Reduced tumor vascularity; encouraging antitumor activity	NCT01688206	126
TREM2	PY314	Anti-TREM2 mAb depleting TREM2⁺ TAMs through ADCC and/or ADCP	Monotherapy; pembrolizumab	I	Recruiting	–	NCT04691375	–

ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; CCL2, C-C motif chemokine ligand 2; CSF1R, colony-stimulating factor one receptor; CTLA-4, cytotoxic T-lymphocyte antigen 4; mAb, monoclonal antibody; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; SoC, standard of care; TAM, tumor-associated macrophage; TREM2, triggering receptor expressed on myeloid cells 2; VEGF, vascular endothelial growth factor.