Table 1.

Phase II/III studies of BRAF-I inhibitors in melanoma.

Study reference	Number of patients eligible for analysis	Study design	Primary end point	Dose and schedule - treatment arm	Responses	Survival	HR (95% CI)
BRIM 2 [22]	132	Phase II, open label	BORR	Vemurafenib (PLX-4032) 960 mg b.i.d. orally	BORR: 52.3% CR: 2.3% PR: 50%	6.2 months	N/A
BRIM 3 [4]	675	Phase III, randomized, double blind	OS	Vemurafenib (PLX-4032) 960 mg b.i.d. orally	PLX-4032: 84% (6 months) DTIC® alone: 64% (6 months)	PLX-4032: 5.3 months DTIC alone: 1.6 months	Death 0.37 (95% CI 0.26 – 0.55) Progression 0.26 (95% CI 0.20 – 0.33)
Infante et al [23]	16 (45)	Three-part Phase I/II Part 1: PK drug-drug interaction study Part 2: dose escalation to find MTD followed by expansion Part 3: randomized Phase II trial in untreated stage IV melanoma	Part 1: PK/PD Part 2: OR	Dabrafenib (GSK2118436, BRAF inhibitor) 75 – 150 mg b.i.d. + GSK1120212 (oral MEK1/2 inhibitor) 1.0, 1.5 or 2.0 mg q.d. RP2D: GSK2118436 150 mg b.i.d. + GSK1120212 2 mg q.d.	ORR: 81% (13 PR + 3 SD)	N/A	N/A

CI: Confidence interval; HR: Hazard ratio; N/A: Not applicable; ORR: Overall response rate; OS: Overall survival; PD: Pharmacodynamics; PFS: Progression-free survival; PK: Pharmacokinetics; PR: Partial response; RP2D: Recommended Phase II dosage; SD: Stable disease.