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Table 1 Combination TAMs-directed therapies with checkpoint blockades in selected clinical trials for cancer therapy

From: Harnessing tumor-associated macrophages as aids for cancer immunotherapy

Action

TAM-targeted agent

Checkpoint blockade

Clinical phase (status)

Tumor type

Effect

Clinical trials

Targeting TAM recruitment and survival

Emactuzumab (CSF1R inhibitor)

Atezolizumab (PD-L1 antibody)

Phase I (Recruiting)

Locally advanced or metastatic solid tumors

NA

NCT02323191

ARRY-382 (CSF1R antagonists)

Pembrolizumab (PD-1 antibody)

Phase I/II (Active, not recruiting)

Advanced solid tumors

NA

NCT02880371

Pexidartinib (anti-CSF1R)

Durvalumab (PD-L1 antibody)

Phase I (Active, not recruiting)

Colorectal cancer; Pancreatic cancer; Metastatic cancer; Advanced cancer

NA

NCT02777710

SNFX-6352 (CSF1R antagonists)

Durvalumab (PD-L1 antibody)

Phase I (Recruiting)

Solid tumor; Metastatic tumor; Locally advanced malignant neoplasm; Unresectable malignant neoplasm

Safe, Well-tolerated

NCT03238027

BLZ945 (CSF1R antagonists)

PDR001 (anti-PD-1; Novartis)

Phase I/II (Recruiting)

Advanced solid tumors

NA

NCT02829723

Cabiralizumab (CSF1R antagonists)

Nivolumab (anti-PD-1)

Phase I (Recruiting)

Advanced malignancies

Safe, Well-tolerated

NCT03158272

AMG820 (CSF1R antagonists)

Pembrolizumab (PD-1 antibody)

Phase I/II (Active, not recruiting)

Pancreatic cancer; Colorectal cancer; Non-small cell lung cancer

NA

NCT02713529

Trabectedin

Durvalumab (PD-L1 antibody)

Phase I (Recruiting)

Ovarian carcinoma; Soft tissue sarcoma

NA

NCT03085225

Reprogramming TAMs to antitumor macrophages

APX005M (CD40 agonistic antibody)

Nivolumab (anti-PD-1)

Phase I/II (Recruiting)

Non-small cell lung cancer; Metastatic melanoma

NA

NCT03123783

Selicrelumab (CD40 agonist)

Atezolizumab (PD-L1 antibody)

Phase I (Recruiting)

Solid tumors

NA

NCT02304393

IPI-549 (PI3Kγ inhibitors)

Nivolumab (anti-PD-1)

Phase I (Recruiting)

Advanced solid tumor; non-small cell lung cancer; melanoma; breast cancer

NA

NCT02637531

TTI-621 (SIRPα-IgG1 Fc)

Nivolumab (anti-PD-1);

Pembrolizumab (PD-1 antibody);

Atezolizumab (PD-L1 antibody);

Durvalumab (PD-L1 antibody)

Phase I (Recruiting)

Solid tumors; melanoma; merkel-cell carcinoma; squamous cell carcinoma; breast carcinoma

NA

NCT02890368

TTI-621 (SIRPα-IgG4 Fc)

Nivolumab (anti-PD-1);

Pembrolizumab (PD-1 antibody);

Phase I (Recruiting)

Lymphoma; myeloma

NA

NCT03530683

GSK3145095 (RIP inhibitor)

Pembrolizumab (PD-1 antibody)

Phase I/II (Recruiting)

Neoplasms; pancreatic

NA

NCT03681951

NKTR262 (TLR7/8 agonist)

Nivolumab (anti-PD-1)

Phase I/II (Recruiting)

Melanoma; merkel cell carcinoma; breast cancer; renal cell carcinoma; colorectal cancer

NA

NCT03435640

  1. NA Not available, CSF1R Colony-stimulating factor 1 receptor, SIRPα Signal regulatory protein alpha, RIP1 Receptor-interacting serine/threonine protein kinase 1, TLRs Toll-like receptors