Table 4.

The clinical trials of signaling pathway inhibitors

Target	Drug name	Com	Num	Regiments	Phase	Status	Object	POM	NCT number
PI3K inhibitor	Alpelisib (BYL719)	nab-paclitaxel	137	Alpelisib: 300 mg qd po nab-paclitaxel: 100 mg/m2 iv on Days 1, 8 and 15 of a 28-day cycle	III	Active, not recruiting	TNBC	PFS, ORR	NCT04251533
	Alpelisib (BYL719)	nab-paclitaxel	8	Alpelisib: qd po on days 1–21 Nab-paclitaxel: iv over 30 min on days 1, 8, and 15	II	Active, not recruiting	TNBC	pCR	NCT04216472
	AZD8186		147	A single dose on day 1 followed by ongoing multiple dosing	I	Completed	TNBC	Safety and tolerability	NCT01884285
	BKM120 (Buparlisib)		50	100 mg/d po in cycles of 28 days	II	Completed	TNBC	CBR	NCT01790932
	BKM120		50	100 mg/d po in cycles of 28 days, until disease progression	II	Completed	TNBC	CBR	NCT01629615
	BKM120	Capecitabine	10	BKM120: 100 mg/d po Capecitabine: 500 mg bid po, 14 days on and 7 days off	II	Completed	mBC	CBR	NCT02000882
	BKM120/BYL719	Olaparib	118	BKM120: 40 mg/d po Olaparib: 50 mg bid po BYL719: 250 mg/d po	I	Completed	TNBC	MTD	NCT01623349
	CUDC-907		43	60 mg/d po 5 days on 2 days off until disease progression	I	Completed	TNBC	Safety and tolerability	NCT02307240
	GDC-0941	Cisplatin	11	GDC-0941: 260 mg po, days 2–6, 9–13, 16–20, 23–27. 28 days cycle Cisplatin: 25 mg/m2 iv day 1, 8, 15	I/II	Terminated	TNBC	Safety and tolerability, ORR	NCT01918306
	SF1126		44	Dose Escalating with 3 + patients in each cohort	I	Completed	Solid cancer	DLTs	NCT00907205
Akt inhibitor	GSK2141795	Trametinib (GSK1120212)	37	GSK2141795: po qd on days 1–28 Trametinib: po qd on days 1–28	II	Completed	TNBC	ORR	NCT01964924
	GSK2141795	Trametinib	240	Po qd	I	Completed	TNBC	Safety and tolerability	NCT01138085
	GSK2141795	Trametinib	37	Po qd on days 1–28	II	Completed	TNBC	ORR	NCT01964924
	ONC201 (TIC10)		4	Po on days 3, 10, and 17	II	Terminated	TNBC	ORR	NCT03733119
	Ipatasertib (GDC-0068)	Paclitaxel	151	Ipatasertib: 400 mg/d po on days 1–21 of each 28-day cycle for 3 cycles Paclitaxel: 80 mg/m2 iv q1w	II	Completed	TNBC	pCR	NCT02301988
	Ipatasertib	Paclitaxel	124	Ipatasertib: 400 mg/d po days 1–21 in each cycle of 28 days Paclitaxel: 80 mg/m2 iv on days 1, 8, and 15	II	Completed	TNBC	PFS	NCT02162719
PI3K /mTOR inhibitor	PF-05212384 (Gedatolisib)	Docetaxel/ Cisplatin	110	90 mg/m2 iv as a 3 weeks cycle Docetaxel/Cisplatin: 75 mg/m2 iv once q3w	I	Completed	TNBC	DLTs, ORR	NCT01920061
	BEZ235	MEK162	29	NA	I	Completed	TNBC	DLTs	NCT01337765
	PQR309	Eribulin (Halaven®)	41	PQR309: after eribulin Eribulin: 1.4 mg/m2 iv on day 1, 8 in a period of 21 days	I	Completed	TNBC	AEs, SAEs	NCT02723877
EGFR inhibitor	Cetuximab (Erbitux)	Ixabepilone (Ixempra ®)	40	Cetuximab: 400 mg/m2 iv over 120 min on day 1 of the first of four 21 days cycles Ixabepilone: 40 mg/m2 iv over 180 min on day 1 of each of four 21 days cycles	II	Completed	TNBC	CRR	NCT01097642
	Lapatinib (Tykerb ®)	Veliparib (ABT-888)	23	Lapatinib:1250 mg/d for 28 days Veliparib: 200 mg/bid for 28 days	NA	Active, not recruiting	TNBC	Safety and toxicity	NCT02158507
	Lapatinib	Everolimus (mTOR inhibitor)	5	Lapatinib: 1250 mg by mouth daily Everolimus: 5 mg by mouth daily	II	Terminated	TNBC	Safety and toxicity, ORR	NCT01272141
	Erlotinib (Tarceva ®)	Cisplatin plus temsirolimus	9	Erlotinib: 100 mg by mouth daily Cisplatin: 30 mg/m2 iv weekly on days 1 and 8 of a 3 weeks cycle Temsirolimus: dosing level, 15 mg, 25 mg	I	Completed	TNBC	MTD	NCT00998036
	Erlotinib	Metformin	8	Erlotinib: 150 mg/d Metformin: 850 mg bid	I	Completed	TNBC	MTD	NCT01650506
	Erlotinib	Bendamustine	11	Erlotinib: 100 or 150 mg po on days 5—21 of each 28 days cycle Bendamustine: 100 or 120 mg/m2 iv on days 1 and 2	I/II	Completed	Breast Cancer	MTD, DLTs, PFS	NCT00834678
	Gefitinib (Irresa ®)		50	250 mg/d by mouth until disease progression	II	Unknown	TNBC	CBR	NCT01732276
Notch inhibitor	AL101		67	NA	II	Active, not recruiting	TNBC	ORR	NCT04461600
	RO4929097 (R4733)		6	Po qd on days 1–3, 8–10, and 15–17	II	Terminated	TNBC	ORR, PFS	NCT01151449
	RO4929097	Carboplatin plus Paclitaxel	14	RO4929097: po qd on days 1–3, 8–10, and 15–17 Paclitaxel: iv over 60 min on days 1, 8, and 15 Carboplatin: iv over 60 min on day 1	I	Terminated	TNBC	AEs, MTD	NCT01238133
TGF-β inhibitor	Bintrafusp Alfa (M7824)		11	1200 mg once q2w	II	Completed	TNBC	ORR	NCT04489940

PIK3: phosphoinositide-3-kinase; TNBC: triple negative breast cancer; PFS: progression-free survival; pCR: pathologic complete response; CBR: clinical benefit rate; MTD: maximum tolerated dose; AKT: serine/threonine kinase; mTOR: mammalian target of rapamycin; EGFR: epidermal growth factor receptor; DLT: dose-limiting toxicity; AEs: adverse events; SAEs: serious adverse events; TGF-β: transforming growth factor Beta; mTNBC: metastatic triple negative breast cancer; HER2-: HER2 negative; mBC: metastatic breast cancer; gBRCA1/2 m: germline BRCA1/2 mutated; ORR: overall response rate; CRR: complete response rate