Table 4 Clinical trials evaluating CAFs directed therapies

JAK/STAT pathway

Ruxolitinib

PDAC

Placebo + Capecitabine

Well tolerated; may improve survival in patients with inflammation (elevated serum C-reactive protein)

Phase II

NCT01423604

[211]

FGFR

Futibatinib (TAS-120)

BC

Fulvestrant

6-month PFS: 45.5% (95% CI: 24.4, 67.8); Median PFS: 7.2 months (95% CI: 2.1, 7.6)

Phase II

NCT04024436

[218]

PDGFR

Imatinib

Neurofibromas

None

ORR: 17%; Imatinib may be effective for treating plexiform neurofibromas in NF1 patients

Phase II

NCT01673009

[124]

CTGF

S-3304

Solid tumors

None

Well tolerated; satisfactory plasma concentrations

Phase I

NCT00033215

[64]

CTGF

Pamrevlumab (FG-3019)

PDAC

Placebo + Gemcitabine/Nab-Paclitaxel

CA 19–9 response (≥ 50% decline from baseline): 65% (experimental) vs 42% (control); Pamrevlumab may enhance gemcitabine/nab-paclitaxel neoadjuvant therapy

Phase I

NCT02210559

[223]

Hedgehog

IPI-926

PDAC

Cetuximab, Gemcitabine, FOLFIRINOX, None

Well tolerated with signs of anti-tumor efficacy; High ORR (67%) in advanced pancreatic adenocarcinoma

Phase I, Ib/II, I, I

NCT01255800

[198]

CXCR4

AMD3100 (Plerixafor)

Glioblastoma, PDAC

Bevacizumab, Cemiplimab

Well tolerated; Plerixafor distributes to CSF and brain tumor tissue; ORR: 19% in pancreatic cancer

Phase I, II

NCT01339039, NCT04177810

[214]

CXCR4

Balixafortide

BC

Eribulin

Well tolerated; Promising efficacy with ORR: 33%

Phase I

NCT01837095

[212]

Tenascin

131I-m81C6

Brain tumors

Chemotherapy

Well tolerated; OS greater than historical controls treated with surgery + iodine-125 brachytherapy

Phase II

NCT00003461

[170]

Hyaluronic acid

PEGPH20

PDAC

Nab-Paclitaxel + Gemcitabine, Eribulin, Nab-Paclitaxel + Gemcitabine

Improved PFS in pancreatic cancer (HA-high tumors); 5/14 PR in breast cancer; Increased ORR but no improvement in OS or PFS in pancreatic adenocarcinoma

Phase II, Ib/II, III

NCT01839487, NCT02753595, NCT02715804

[182]

Vitamin D metabolism

Paricalcitol

BC

Chemotherapy

Well-tolerated

Phase I

NCT00637897

[240]

Angiotensin receptor

Losartan

PDAC

Hypofractionated radiation therapy after chemotherapy

No results posted yet

Phase I

NCT04106856

N/A

TGF-β

LY3200882

Solid tumors

Gemcitabine

Safe and well-tolerated; 6/12 PR, 3/12 stable disease; Overall DCR: 75%

Phase I

NCT02937272

[210]

FAP

131I-Sibrotuzumab

FAP + cancer

None

Repeated infusions administered safely

Phase I

NCT02209727

[231]