Table 4.

Clinical trials of horizontal inhibition of MAPK and PI3K pathways and targeted therapy in advanced solid tumors

Molecular targets, therapeutic agentsStudyaPhasePatient populationTrial statusa,b
BRAF inhibitor + PI3K inhibitor
 Vemurafenib + buparlisibNCT01512251 (115)1/2BRAF V600E/K–mutated unresectable or MMUnknown
 Vemurafenib + PX-866NCT016161991/2BRAF-mutated advanced cancer, including melanomaTerminated due to slow accrual
 Vemurafenib + SAR260301NCT016737371Advanced solid tumors and unresectable or metastatic BRAF-mutated melanomaCompleted
MEK inhibitor + PI3K inhibitor
 Trametinib + buparlisibNCT011554531bSelected advanced solid tumorsCompleted
 Binimetinib + buparlisibNCT013632321bSelected advanced solid tumorsOn-going
 Cobimetinib + pictilisibNCT00996892 (80)1bLocally advanced or metastatic solid tumorsTerminated
 Refametinib + copanlisibNCT01392521 (81)1bAdvanced solid tumorsCompleted
 Binimetinib + alpelisibNCT014490581b/2Selected advanced solid tumorsOn-going
 WX-554 + WX-037NCT018593511Advanced solid tumorsTerminated
BRAF inhibitor + mTOR inhibitor
 Vemurafenib + everolimus or temsirolimusNCT01596140 (116)1BRAF-mutated advanced cancer, including melanomaOn-going
MEK inhibitor + mTOR inhibitor
 Trametinib + everolimusNCT00955773 (85)1bAdvanced solid tumorsCompleted
 Pimasertib + temsirolimusNCT01378377 (86)1Advanced solid tumorsCompleted
MEK inhibitor + Dual PI3K/mTOR inhibitor
 Binimetinib+ dactolisibNCT013377651bSelected advanced solid tumorsCompleted
 Trametinib + omipalisibNCT012488581Advanced solid tumorsTerminated
 Pimasertib + voxtalisibNCT01390818 (88)1bLocally advanced or metastatic solid tumorsCompleted
 PD-0325901 + PF-04691502NCT01347866 (117)1Advanced solid tumorTerminated due to internal portfolio review
MEK inhibitor + AKT inhibitor
 Trametinib + afuresertibNCT01476137 (11)1/2Solid tumor malignancy, including melanoma and multiple myelomaCompleted
 Trametinib + uprosertibNCT01941927 (118)2BRAF-WT unresectable stage III or IV melanomaOngoing, not recruiting
NCT01138085 (119)1Solid tumor with KRAS or BRAF mutation or none specified dependent on tumor typeCompleted
NCT01964924 (89)2Advanced TNBCOngoing
 Selumetinib + MK-2206NCT01021748 (90)1Locally advanced or metastatic solid tumors and expansion in KRAS-mutated solid tumorsCompleted
NCT015194272BRAF V600–mutant unresectable, stage III or IV melanoma that had progressed after therapy on selective BRAF inhibitorTerminated due to slow enrollment
 Cobimetinib + ipatasertibNCT01562275 (91)1bLocally advanced or metastatic solid tumorsCompleted
BRAF + MEK + AKT inhibitors
 Dabrafenib + trametinib + uprosertibNCT019021731/2BRAF V600–mutated unresectable or metastatic solid tumors, including melanoma, stage IIIC or IVTemporarily stopped for assessment