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Table 1 Summary of the basic profile of type I AXL inhibitors and the related ongoing clinical trials

From: AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Drug

Developer

Target(s)a

IC50 for AXL

Clinical Trial No.b

Phase of approval

Indications

Monotherapy/Combinations

Adverse events

Status

BGB324 (R428)

Rigel Pharmaceuticals/BerGen BIO

AXL (selective)

IC50 (in vitro) = 14 nM

IC50 (in cells) = 14 nM

NCT02424617

I/II

NSCLC

+ Erlotinib

Not reported

Recruiting

NCT03184558

II

TNBC

+ Pembrolizumab

 

Recruiting

NCT02488408

Ib/II

AML, MDS

± Cytarabine/decitabine

 

Recruiting

NCT02872259

Ib/II

Metastatic melanoma

+ Pembrolizumab; + Dabrafenib and trametinib

 

Recruiting

NCT03649321

Ib/II

Pancreatic cancer

± Nab-paclitaxel/gemcitabine/cisplatin

 

Recruiting

NCT03824080

II

MDS

Monotherapy

 

Recruiting

TP-0903

Tolero Pharmaceuticals

AXL (selective)

IC50 (in vitro) = 27 nM

IC50 (in cells) = 222 nM

NCT03572634

I/II

CLL

± Ibrutinib

Not reported

Not yet recruiting

NCT02729298

I

Advanced solid tumors

Monotherapy

 

Recruiting

Crizotinib (PF-02341066, marketed as [Xalkori])

Pfizer

MET, ALK, RON, AXL

IC50 (in vitro) = 294 nM

IC50 (in vivo) = 322 nM

NCT02737501

III

ALK-positive locally advanced or metastatic NSCLC

Crizotinib vs. Brigatinib

Abdominal pain, headache, pyrexia, pain in extremity, nausea

Active, not recruiting

NCT02223819

II

Uveal melanoma

Monotherapy

Active, not recruiting

NCT02435108

II

MET-positive gastric cancer

Monotherapy

Completed

NCT02207504

I

Castration-resistant prostate cancer

+ Enzalutamide

Active, not recruiting

Bosutinib (SKI-606, Bosulif®)

Pfizer

ABL, SRC, AXL

IC50 (in vitro) = 174 nM

NCT02228382

IV

Previously treated Ph + CML

Monotherapy

Diarrhea, rash, liver enzyme elevations

Active, not recruiting

NCT03106779

III

CML

Bosutinib vs. ABL001

Recruiting

NCT01331291

II

Glioblastoma

Monotherapy

Completed

NCT00319254

II

Breast cancer

Monotherapy

Completed

NCT03023319

I

Metastatic solid tumors

+ Pemetrexed

Recruiting

Gilteritinib (ASP2215)

Astellas Pharma/Kotobuki Pharmaceutical

FLT3, AXL

IC50 (in vitro) = 0.73 nM

NCT02927262

III

Relapsed or treatment refractory FLT3 mutated AML

Gilteritinib or placebo

Febrile neutropenia, anemia, thrombocytopenia, sepsis, pneumonia, diarrhea, fatigue, elevated aspartate aminotransferase and alanine aminotransferase

Recruiting

NCT02456883

I

Advanced solid tumors

Monotherapy

Completed

NCT02495233

I/II

NSCLC

+ Erlotinib

Terminated

S49076

Servier

MET, MER, AXL FGFR3

IC50 (in vitro) = 7 nM

IC50 (in cells) = 56 nM

ISRCTN00759419

I

Advanced solid tumors

Monotherapy

Peripheral oedema and hypoalbuminaemia

Completed

Amuvatinib (MP-470)

Astex Pharmaceuticals

KIT, AXL, PDGFR1, FLT3, RET

IC50 (in vitro) = 10 nM

NCT01357395

II

SCLC

Monotherapy

Fatigue, alopecia, diarrhea, nausea, anorexia, neutropenia, anemia, thrombocytopenia, leukopenia

Completed

NCT00894894

I

Solid tumors

Monotherapy

Completed

NCT00504205

Not Applicable

Unresectable or metastatic solid tumor or lymphoma

Monotherapy

Terminated

Sunitinib (SU11248, marketed as Sutent)

Pfizer

PDGFR, VEGFR2, FLT3, KIT, AXL

IC50 (in vitro) = 5 nM

NCT00706706

IV

Metastatic RCC

Monotherapy

Diarrhea, fatigue, hypertension, palmar-plantar erythrodysesthesia, and hematologic adverse events

Completed

NCT02691793

IV

Refractory Solid Tumors

Monotherapy

Recruiting

NCT01525550

IV

Pancreatic neuroendocrine tumor

Monotherapy

Completed

NCT00793871

IV

GIST

Monotherapy

Completed

NCT00794950

II

Urothelial carcinoma

Monotherapy

Active, not recruiting

NCT01718327

II

Unresectable and advanced cholangiocarcinoma

Monotherapy

 

Completed

NCT01824615

II

Ovarian cancer

Monotherapy

 

Completed

NCT02623127

II

Thymic carcinoma

Monotherapy

 

Completed

NCT00372775

II

NSCLC

Monotherapy

 

Completed

NCT01498835

I

Soft tissue sarcoma

Monotherapy

 

Completed

SNS314

2-D08

Sunesis Pharmaceuticals

Aurora A/B/C, Trk A/B, FLT4, Fms, Axl

IC50 (in vitro) = 84 nM

NCT00519662

I

advanced solid tumors

Monotherapy

Not reported

Completed

AXL, IRAK4, ROS1

IC50 (in vitro) = 0.49 nM

–

–

–

–

–

Preclinical

UNC2025

University of North Carolina

MER, FLT3, AXL, Tyro3

IC50 (in vitro) = 14 nM

–

–

–

–

–

Preclinical

SGI-7079

Tolero Pharmaceuticals/Astex Pharmaceuticals

AXL (selective)

IC50 (in vitro) = 58 nM

IC50 (in vivo) < 1 uM

–

–

–

–

–

Preclinical

UNC569

 

MER, AXL, Tyro3

IC50 (in vitro) = 37 nM

–

–

–

–

–

Preclinical

NA80x1

 

AXL (selective)

IC50 (in vitro) = 12.67 ± 0.45 μM, IC50 (in vivo) = 4.11 ± 1.47uM

–

–

–

–

–

Preclinical

DP-3975

Deciphera Pharmaceuticals, LLC

AXL (selective)

IC50 (in vitro) = 100 nM ∼ 2 uM

–

–

–

–

–

Preclinical

  1. Abbreviations: NSCLC non-small cell lung cancer, TNBC triple-negative breast cancer, AML acute myeloid leukemia, MDS myelodysplastic syndrome, CLL chronic lymphocytic leukemia, CML chronic myelogenous leukemia, FLT3 FMS-like tyrosine kinase 3, GIST gastrointestinal stromal tumors, RCC renal cell carcinoma, SCLC small cell lung cancer
  2. aIn the order of inhibition potency
  3. bAll the relevant information of clinical trials can be found on the public clinical trial registry website (clinicaltrials.gov). Here is a partial list of all the relevant clinical trials
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Molecular Cancer

ISSN: 1476-4598