Table 4: Phase II/III studies of newer targeted agents.

Study referenceNo. of patients eligible for analysis (followup)Study designPrimary endpointDose and schedule—treatment armORR/OSPFS (mths)HR (95% CI)

BMS 008 [100]155Phase II, open-label, single armDose findingIpilimumab—10 mg/kg47% (1 yr)N/AN/A

BMS 022 [101]217Phase II, randomized, double blindTo evaluate the efficacy of three dose levels of ipilimumabIpilimumab—10 mg/kg48% (1 yr)N/AN/A

BMS 007 [102]115Phase II, randomized, double blindTo evaluate the rate of grade 2 + diarrheaIpilimumab—10 mg/kg51% (1 yr)N/AN/A

Medarex MDX010-20 [3]676Phase III, randomized, double blindORR, subsequently amended to OSIpilimumab—3 mg/kgIpi alone: 10.1 mths (95% CI 8.0 to 13.8)
Ipi + GP-100: 10.0 mths (95% CI 8.5 to 11.5)
GP-100 alone: 6.4 mths (95% CI 5.5 to 8.7)
Ipi alone: 2.86 mths (95% CI 2.76 to 3.02)
Ipi + GP-100: 2.76 mths (95% CI 2.73 to 2.79)
GP-100 alone: 2.76 mths (95% CI 2.73 to 2.83)
Ipi alone (compared to GP-100 alone):0.66 (95% CI 0.51-0.87)
Ipi + GP-100 (compared to GP-100 alone):0.68 (95% CI 0.55-0.85)

BMS 024 [103]502Phase III, randomized, double blindOSIpilimumab + DTIC: Induction—IPI 10 mg/kg + DTIC (850 mg/m2) q3 weeks for 4 doses Maintenance—IPI 10 mg/kg + DTIC (850 mg/m2) q12 weeksIpi + DTIC: 47.3% (1 yr), 28.5% (2 yr), 20.8% (3 yr)
DTIC alone: 36.3% (1 yr), 17.9% (2 yr), 12.2% (3 yr)
Ipi + DTIC: 2.8
DTIC alone: 2.6
Ipi + DTIC:
OS 0.72
PFS 0.76

BRIM 2 [104]132Phase II, open labelBORRVemurafenib (PLX-4032) 960 mg twice daily orallyBORR: 52.3%
CR: 2.3%
PR: 50%
6.2N/A

BRIM 3 [5]675Phase III, randomized, double blindOSVemurafenib (PLX-4032) 960 mg twice daily orallyPLX-4032: 84% (6 mos)
DTIC alone: 64% (6 mos)
PLX-4032: 5.3
DTIC alone: 1.6
Death 0.37 (95% CI 0.26 to 0.55)
Progression 0.26 (95% CI 0.20 to 0.33)

Key: N/A—not applicable.