Table 3

Clinical trials of TAM reprogrammingagents in EOC

Target	Agent	Mechanism of action	Combination partners	Phase	Status	Results	Identifier	Ref.
TLR7	852A	TLR7 agonist inducing the activation of innate immune cell populations	Monotherapy	II	Completed	↑immune cell activation - ↑CXCL10↑IL-1ra; modest clinical benefit	NCT00319748	135
TLR8	Motolimod	TLR8 agonist inducing the activation of innate immune cell populations	PLD; paclitaxel	I	Completed	–	NCT01294293	–
TLR8			PLD	II	Completed	Improved OS in patients with ISRs	NCT01666444	136
TLR9	Vidutolimod (CMP-001)	VLP-encapsulated TLR9 agonist	Anti-PD-L1 mAb avelumab; avelumab+anti-4-1BB mAb utomilumab; avelumab+anti-OX40 mAb	II	Active	–	NCT02554812	–
PI3Kγ	Eganelisib (IPI-549)	Selective PI3Kγ inhibitor reprogramming key immune suppressive cells	Monotherapy; nivolumab	I	Active	–	NCT02637531	–
PI3Kγ			Dual adenosine receptor antagonist etrumadenant (AB928)+PLD	I	Completed	–	NCT03719326	–
CD40	Selicrelumab	Agonistic anti-CD40 mAb potentiating APC functions	Paclitaxel+carboplatin	I	Completed	Evidence of antitumor activity with 20% of patients displaying PRs	NCT00607048	146
			Bevacizumab; bevacizumab+vanucizumab	I	Completed	–	NCT02665416	–
	CDX-1140	Agonistic anti-CD40 mAb potentiating APC functions	Monotherapy; gemcitabine+paclitaxel; pembrolizumab or FLT3L	I	Active	–	NCT03329950	–
			Pembrolizumab+bevacizumab	II	Not yet recruiting	–	NCT05231122	–
IL-12	GEN-1	IL-12 plasmid/lipopolymer complex stimulating the antitumor immune responses	Neoadjuvant paclitaxel+carboplatin	I	Completed	↑IL-12, IFN-γ; ↑CD8⁺ T cells and ↓immunosuppression in the TME; preliminary clinical activity	NCT02480374	155
IL-12			Neoadjuvant paclitaxel+carboplatin	II	Recruiting	–	NCT03393884	–
HER2	CT-0508	CAR macrophages targeting HER2⁺ tumor cells	Monotherapy	I	Recruiting	–	NCT04660929	–
CD47	AO-176	Antagonistic anti-CD47 mAb promoting phagocytosis and direct tumor cell killing	Monotherapy; paclitaxel; pembrolizumab	I/II	Recruiting	–	NCT03834948	–
	Magrolimab (Hu5F9-G4)	Antagonistic anti-CD47 mAb promoting phagocytosis and direct tumor cell killing	Monotherapy	I	Completed	PRs in 2 out of 13 OC patients; ↓CA125	NCT02216409	167
			Avelumab	I	Completed	–	NCT03558139	–
			Anti-EGFR mAb cetuximab	I/II	Completed	↑TAM infiltration; disease stabilization in some patients	NCT02953782	166
	TTI-622	Fusion protein blocking CD47	PLD	I/II	Recruiting	–	NCT05261490	–
	SL-172154	Fusion protein targeting CD47 on tumor cells and CD40 on APCs		I	Recruiting	–	NCT04406623	–
CD47/mesothelin	NI-1801	Anti-CD47/mesothelin bispecific mAb	Monotherapy	I	Recruiting	–	NCT05403554	–
CD47/PD L1	PF-07257876	Anti-CD47/PD-L1 bispecific mAb	Monotherapy	I	Recruiting	–	NCT04881045	–
SIRPα	BI-765063	antagonistic anti-SIRPα mAb	Anti-PD-1 mAb ezabenlimab	I	Recruiting	–	NCT03990233	–
IDO	Epacadostat	IDO inhibitor restoring the activation of immune cells	Monotherapy	II	Terminated	Lack of evidence of superiority	NCT01685255	176
			CRS-207 (Listeria-based vaccine expressing human mesothelin); CRS-207+pembrolizumab	I/II	Terminated	Lack of clinical activity	NCT02575807	–
			Pembrolizumab	II	Terminated	–	NCT03602586	–
			Monotherapy	I	Active	–	NCT02042430	–
			Nivolumab; nivolumab+chemotherapy	I/II	Completed	–	NCT02327078	–

APC, antigen-presenting cell; CAR, chimeric antigen receptor; CXCL10, C-X-C motif chemokine ligand 10; EGFR, epidermal growth factor receptor; FLT3L, FMS-like tyrosine kinase three ligand; HER2, human epidermal growth factor receptor 2; IDO, indoleamine 2,3-dioxygenase; IFN, interferon; ISR, injection site reaction; mAb, monoclonal antibody; OC, ovarian cancer; OS, overall survival; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; PI3Kγ, phosphatidylinositol 3-kinase γ; PLD, pegylated liposomal doxorubicin; PR, partial response; SIRPα, signal regulatory protein α; TAM, tumor-associated macrophage; TLR, toll-like receptor; TME, tumor microenvironment; VLP, virus-like particle.