Table 1:

Clinical Trials of Trametinib in melanoma

Trial	Phase	Target	Drug	Study population		PFS	RR	Remarks
Infante et.al [26]	I	MEK	Trametinib	Advanced solid tumors N=206	Pancreatic (n=26) Colorectal (n=28) NSCLC (n=30) Melanoma (n=97) Others (n=25)	-	10%	MTD =3 mg daily RP2D = 2mg daily
Falchook et.al [32]	I	MEK	Trametinib	Metastatic Melanoma N=97	BRAF mutant (n=36)  BRAFi naïve (n= 30)  Prior BRAFi (n=6) BRAF wild (n=39) BRAF unknown (n=6) NRAS mutant (n=7) Uveal melanoma (n=16)	5.7 NA 2 NA NA 1.8	40% NA 10% 0% 0% 0%	Concurrent BRAFV600 WT/NRAS WT (n=20) had a trend of higher RR (20%) than BRAFV600WT/NRAS-mutant patients
Kim et.al [47]	II	MEK	Trametinib	BRAF mutant Metastatic N=97	BRAFi therapy (n= 40) BRAFi naïve (n=57)	1.8 4	0% 25%	stable disease =28% stable disease =51%
Flaherty et.al [14]	III	MEK	Trametinib vs. Chemo	BRAF mutant Metastatic N=322	Trametinib (n= 214) Chemotherapy (n= 108)	4.8 1.5	22% 8%	6 month OS = 81% vs, 67% stable disease = 56% vs. 31%
Flaherty et.al [15]	I/II	BRAF MEK	Dabrafenib/ Trametinib	BRAF V600 mutant Metastatic N=162	DT 150/2 (n =54) DT 150/1 (n=54 D150 (n=54)	9.4 9.2 5.8	76% 50% 54%
Long et.al [18]	III	BRAF MEK	Dabrafenib/ Trametinib vs. Dabrafenib	BRAF V600E/K N=423	DT (n=211) D (n=212)	9.3 8.8	67% 55%
Robert et.al [19]	III	BRAF MEK	Dabrafenib/ Trametinib vs. Vemurafenib	BRAF V600E/K N=604	DT (n=352) V (n=352)	11.4 7.3	64% 51%	12 month OS 72% vs. 67%

PFS- progression free survival (in months); RR- response rates; NSCLC- Non small cell lung cancer; MTD-Maximum Tolerated Dose; RP2D- Recommended phase 2 dose; WT- wild type; BRAFi – BRAF inhibitor; n- number of patients; OS- overall survival