. 2020 Dec 9;10:599933. doi: 10.3389/fonc.2020.599933

Table 2.

Targeting drugs under investigations (based on www.clinicaltrials.gov at 05/25/2020).

Targeting drug	Name	Spectrum	Results	Status	Clinical Trials
Targeted cytotoxic drug
CD33	gemtuzumab ozogamicin	CD33+	Relapse risk reduction (HR 0.81), 5 year-OS improvement (HR 0.90)	FDA approval	25 recruiting studies in association
	SGN-CD33A (vadastuximab talirine)	CD33+	Higher rate of death	Terminated	NCT02785900
	lintuzumab-Ac225	CD33+	Under investigations	Phase 1 & phase 1/2	NCT03441048, NCT03867682
CD123	IMGN632		Under investigations	Phase 1/2	NCT04086264, NCT03386513
Epigenic-directed therapies
IDH1	ivosidenib	IDH1^mut	R/R AML: CR/CRi 30.4%, ORR 41.6% (phase 1)	FDA approval	9 recruiting studies alone or in association
IDH2	enasidenib	IDH2^mut	R/R AML: CR 19.6%, ORR 38.8% (phase 1/2)	FDA approval	12 recruiting studies alone or in association
HDAC	panobinostat		Limited benefit	Phase 3	NCT04326764
	vorinostat		Limited benefit	Phase 1 & phase 1/2	NCT03263936, NCT03843528, NCT03878524, NCT03842696
	belinostat		Under investigations	Phase 1	NCT03772925
	entinostat		Under investigations	Phase 2	NCT01305499
EZH2	DS-3201b		Under investigations	Phase 1	NCT03110354
DOT1L	pinometostat	MLL^mut	Under investigations	Phase 1/2	NCT03724084, NCT03701295
KDM1A	tranylcypromine		Under investigations	Phase 1	NCT02273102
KDM1A	INCB059872		Under investigations	Phase 1	NCT02712905
BET	OTX015	MLL^mut	Study withdrawn	Phase 1	NCT01713582, No further study
BET	GSK525762		Under investigations	Phase 2	NCT01943851
BCOR	crizotinib	BCOR^mut	Under investigations	Phase 2	NCT02638428
BCL2	venetoclax	NPM1^mut IDH1/2^mutTP53^mut	In association to HMA in AML ineligible: CR/CRi 67%	Phase 3	56 recruiting studies in association
TP53	elesclomol	TP53^mut	Under investigations	Phase 1	NCT01280786
XPO-1	selinexor	NPM1^mut	Under investigations	Phase 1	NCT02091245, NCT02093403, NCT02299518
Kinase inhibitors
FLT3	midostaurin	FLT3^mut	Front line FLT3^mut-AML: OS 74.7 months (HR 0.78)	FDA approval	13 recruiting studies alone or in association
	sorafenib	FLT3^mut	Largest prospective studies but significative toxicities	Phase 2	12 recruiting studies in association
	gilteritinib	FLT3^mut	Phase 3: OS 9.3 months vs 5.6 months (HR=0.64), CR/Cri 34%	FDA approval	9 recruiting studies in association
	quizartinib	FLT3^mut	Limited benefit	FDA refusal	9 recruiting studies in association
	crenolanib	FLT3^mut	Sensibility despite FLT3-D835 mutation	Phase 2 & 3	NCT03258931, NCT03250338, NCT02400255
MAPK	vemurafenib	NRAS^mut	Under investigations	Phase 1 & 2	NCT03878524, NCT02638428
	pazopanib	NRAS^mut	Under investigations	Phase 2	NCT02638428
	tivozanib	NRAS^mut	Sensibility	Pre-clinical	None
mTOR	everolimus	RUNX1^mut	Under investigations	Phase 1/2	NCT02109744
PIK3C-mTOR	dactolisib	RUNX1^mut	Sensibility	Pre-clinical	None
VEGFR	cediranib	MLL^mut	No confirmed responses	Phase 2	NCT00475150, no further study
BTK/TEC	ibritinib	FLT3^mut ± NPM1^mut	Under investigations	Phase 2	NCT02351037, NCT03267186
SYK	entospletinib	FLT3^mut	Under investigations	Phase 1/2	NCT02343939, NCT03135028, NCT03013998
JAK2	ruxolitinib	JAK2^mut	Under investigations	Phase 1/2	NCT03558607, NCT02257138
	ruxolitinib + decitabine	BCOR^mut	Under investigations	Phase 2	NCT04282187
	ruxolitinib + venetoclax	RUNX1^mut	Under investigations	Phase 1	NCT03874052
IRAK1/4-FLT3-JAK2	pacritinib		Anti-AML activity but stopped due to financial constraints	Terminated	NCT02532010
IRAK4	CA-4948		Under investigations	Phase 1	NCT04278768, NCT03328078

Overview of targeting drug studied in AML. Mut, mutation. R/R AML, relapse and refractory AML. OS, overall survival. CR, complete response. CRi, complete response with incomplete hematological recovery response. ORR, overall response rate. FDA, Food and Drug Administration.