Table 3.

Clinical trials of vertical inhibition of MAPK pathway and targeted therapy in advanced solid tumors

Molecular targets, therapeutic agentsStudyaPhasePatient populationTrial statusa,b
BRAF + MEK inhibitors
Dabrafenib + trametinibBRF113220 (NCT01072175) (42, 105)1/2BRAF V600–mutated unresectable or MMAchieved primary outcome; ongoing pt follow-up
COMBI-d (NCT01584648) (6, 43)3BRAF V600E/K–mutated unresectable or MM, stage IIIC or IVAchieved primary outcome; ongoing pt follow-up
COMBI-v (NCT01597908) (7, 106)3BRAF V600E/K–mutated unresectable or MM, stage IIIC or IVAchieved primary outcome; ongoing pt follow-up
NCT019782362BRAF V600E/K–mutated melanoma with active brain metastasesOngoing
NCT020399472BRAF V600–mutated melanoma with active brain metastasesOngoing
Neoadjuvant (NCT01972347) (107)2BRAF V600–mutated melanoma stage IIIB/COngoing
Neoadjuvant and adjuvant (NCT02231775) (107)2BRAF V600E/K–mutated clinical stage III or oligometastatic melanomaOngoing
BRF113928 (NCT01336634)2BRAF V600E–mutant metastatic NSCLCOngoing
Vemurafenib + cobimetinibBRIM-7 (NCT01271803) (108, 109)1bBRAF V600–mutated unresectable or MM, stage IIIC or IVAchieved primary outcome; ongoing pt follow-up
coBRIM (NCT01689519) (8, 44)3BRAF V600–mutated unresectable or MM, stage IIIC or IVAchieved primary outcome; ongoing pt follow-up
coBRIM-B (NCT02230306) (110)2BRAF V600–mutated melanoma with active brain metastasesTerminated
NEO-VC (NCT02303951)2BRAF V600–mutated melanoma with limited metastasis of MM, stage IIIC or IV, in neoadjuvant settingOngoing
NCT020360862BRAF V600–mutated melanoma with palpable lymph node metastases, in neoadjuvant settingOngoing
CONVERCE (NCT02537600)2BRAF V600–mutated stage IV melanoma with brain metastasisOngoing
Encorafenib + binimetinibNCT01543698 (111, 112)1b/2BRAF V600–mutated unresectable or MM, stage IIIB to IVAchieved primary outcome; ongoing pt follow-up
COLUMBUS (NCT01909453) (45)3BRAF-mutated unresectable or MM, stage IIIB/C or IVAchieved primary outcome; ongoing pt follow-up
MEK + ERK1/2 inhibitors
Cobimetinib + GDC-0994NCT024577931bLocally advanced or metastatic solid tumorsOngoing
Dual RAF/MEK inhibitor
RO5126766NCT00773526 (55)1Select advanced solid tumorsCompleted
NCT024075091Select advanced solid tumorsOngoing
BRAF + CDK4/6 inhibitors
Vemurafenib + voruciclibNCT01841463 (69)1BRAF-mutated unresectable or MM, stage III or IVSuspended after enrollment of 9 patients (2 dose-escalation cohorts) for nonmedical reasons; MTD not reached
Encorafenib + ribociclibNCT017777761b/2BRAF-mutated unresectable or MM, stage III or IVTerminated for nonmedical reasons
MEK + CDK4/6 inhibitors
Trametinib + palbociclibNCT020650631/2BRAF-WT advanced solid tumorsTerminated
PD-0325901 + palbociclibNCT020229821/2KRAS-mutant NSCLC, solid tumorsOngoing
Binimetinib + ribociclibNCT01781572 (70)1b/2NRAS-mutant MMOngoing
MAPK pathway inhibitor + growth factors and/or their receptors tyrosine kinases (GFR/RTK) inhibitors
Multi-RTK inhibitors ± BRAF or MEK or BRAF + MEK inhibitors
 RAF265NCT003045252Locally advanced or metastatic melanomaCompleted
 Binimetinib + RAF265NCT013522731RAS or BRAF V600E–mutated advanced solid tumorsCompleted
 Refametinib + regorafenibNCT021687771b/2Locally advanced or metastatic solid tumorsTerminated
 Dabrafenib + pazopanibNCT01713972 (113)1BRAF-mutated advanced malignant tumorsOngoing
 Vemurafenib + cabozantinibNCT018351841BRAF V600–mutated unresectable or metastatic solid tumor malignancyTerminated
 Trametinib + pazopanibNCT01438554 (114)1Advanced solid tumorsOn-going
BRAF/multi-kinase inhibitor/MEK inhibitor + selective RTK inhibitors
 Lenvatinib + golvatinibNCT014339911/2Unresectable stage III or IV melanoma after prior systemic therapyOngoing
 Vemurafenib and/or cobimetinib + onartuzumabNCT019742581bBRAF V600–mutated unresectable or MM, stage IIIC or IVWithdrawn prior to enrollment
 Sorafenib + tivantinibNCT00827177 (61)1Locally advanced, inoperable, or metastatic solid tumors, including melanomaCompleted
 Sorafenib + bevacizumabNCT003877512Unresectable stage III or stage IV malignant melanomaCompleted
NCT006325412Metastatic breast cancerTerminated
 Vemurafenib + cobimetinib + bevacizumabNCT014959882BRAF V600–mutated unresectable or MM, stage IVTerminated
 Binimetinib + ganitumabNCT015628991b/2Selected advanced solid tumorsTerminated due to nonmedical reasons
 Cobimetinib + MEHD7945ANCT019861661Locally advanced or metastatic cancer with mutant KRASCompleted
  • Abbreviation: pt, patient.

  • aAll studies listed are identified in clinicaltrials.gov. Trial status based on clinicaltrials.gov status, accessed January 25, 2017.

  • bOngoing trials include trials currently recruiting and those not actively recruiting patients.