Table 1 Clinical trials targeting TANs and/or its correlating agents

RTK

Regorafenib

II

Regorafenib showed an encouraging OS benefit in recurrent GB

NCT02926222

[129]

VEGF

Bevacizumab

III

The addition of bevacizumab to RT-TMZ did not improve survival in patients with GB but improved PFS. However, the rate of adverse events was higher with bevacizumab than with placebo

NCT00943826

[127]

N/A

First-line use of bevacizumab did not improve OS in patients with newly diagnosed GB. PFS was prolonged but did not reach the prespecified improvement target

NCT00884741

[128]

PD-1/VEGF

Nivolumab/

Bevacizumab

III

Mediate OS was comparable between nivolumab and bevacizumab in the overall patient population with recurrent GB

NCT02017717

[130]

PD-1

Nivolumab

III

Nivolumab added to RT + TMZ did not improve survival in patients with newly diagnosed GB with methylated or indeterminate MGMT promoter

NCT02667587

[126]

II

Neoadjuvant nivolumab supporting a local immunomodulatory effect of treatment

NCT02550249

[134]

Nivolumab, pembrolizumab

Early phase

Neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response

N/A

[133]

Pembrolizumab

Ib

Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with manageable toxicity in this small, signal-finding, recurrent GB cohort

NCT02054806

[131]

Pembrolizumab with oncolytic DNX-2401

I/II

The combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefits in select patients

NCT02798406

[135]

PD-L1 & VEGF

Durvalumab & Bevacizumab

II

PD-L1 blockade and combination with standard or reduced dose bevacizumab was ineffective

N/A

[132]

PD-L1 & CTLA-4

Nivolumab & Ipilimumab

I

Intracerebral administration of nivolumab and ipilimumab following maximal safe resection of recurrent GB was feasible, safe, and associated with encouraging OS

NCT03233152

[136]

IL-8 (CXCL8)

BMS-986253

Early phase & I

BMS-986253 reduces IL-8 levels, neutrophils recruitment and attenuates mesenchymal transition

NCT02536469

[137, 138]

CXCR2

MK-7123

II

Blocking CXCR2 reduced neutrophil counts and improved lung function in COPD patients

NCT01006616

[139]

Reparixin & Paclitaxel

Ib/II

Weekly paclitaxel plus reparixin in MBC appeared to be safe and tolerable, with demonstrated responses in the enrolled population

NCT02001974

NCT02370238

[140]

SB225002

Early phase

The CXCR2-antagonist inhibited glioma growth during tumor initiation and progression, whereas treatment was well-tolerated by the recipients

N/A

[141]

TGF-β

Galunisertib

Ib/IIa

Adding galunisertib into TMZ-based radiochemotherapy has no differences in efficacy, safety, or pharmacokinetic variables

NCT01220271

[143]

II

Galunisertib + lomustine failed to demonstrate improved OS relative to placebo + lomustine

NCT01582269

[145]