Prior treatment with a MEK inhibitor or ERK inhibitor
Prior systemic therapy with a MEK inhibitor
Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other EGFR inhibitors
Prior treatment with a MEK, Ras or Raf inhibitor
Prior navitoclax, BRAF inhibitor, and MEK inhibitor is prohibited; (exceptions for Phase I are described above)
Prior treatment with cobimetinib or a MEK inhibitor
Previous treatment with cobimetinib or any other mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor
Prior treatment with selumetinib or another specific MEK 1/2 inhibitor
If BRAFV600-mutant, refractory disease to at least one BRAF inhibitor and a MEK inhibitor (defined as progression while on treatment), or intolerance to these drugs
STRATUM B: Previous exposure to a MEK inhibitor (i.e., trametinib, selumetinib)
Prior therapy with a MEK inhibitor
Previous mitogen-activated protein kinase kinase (MEK) inhibitor use such as PD-0325901; CI1040; AS73026; GDC 0973; ARRY43182; GSK110212
Prior treatment with MEK inhibitor
Prior MEK inhibitor therapy is allowed
Prior treatment with a MAP-kinase pathway inhibitor (RAS, RAF, ERK, MEK)
Prior therapy with selumetinib or another specific mitogen-activated protein kinase kinase (MEK) inhibitor is not permitted
Previous MEK, retrovirus associated sequence (RAS), or RAF inhibitor use
Prior treatment with a BRAF inhibitor or a MEK inhibitor; treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and initiation of protocol therapy is observed
Prior treatment with selumetinib or another specific MEK 1/2 inhibitor
Prior treatment with a mitogen-activated protein kinase kinase (MEK) inhibitor
Previous treatment with any MEK inhibitor
Any prior treatment with either a MEK, Ras, or Raf inhibitor for advanced or metastatic NSCLC.
Prior therapy with a MEK inhibitor
Part B: Prior treatment with a RAF or MEK pathway inhibitor, except BRAFmutant melanoma (Group 1)
Prior treatment with 1 BRAF inhibitor and/or 1 MEK inhibitor allowed
No history of prior exposure to a MEK inhibitor
Past treatment with any MEK or ERK inhibitor or with panitumumab
Prior MEK inhibitor or prior TAS-102 therapy
Previous MEK, RAS, or RAF inhibitor use
If BRAFV600-mutant, documented refractory disease to at least one BRAF inhibitor (dabrafenib or vemurafenib) and/or a MEK inhibitor (trametinib or cobimetinib), defined as progression of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria while on treatment; subjects with MAPK inhibitor-intolerance are eligible if they meet criteria
Patients who have prior therapy with trametinib or any other MEK inhibitor
Subjects with B-Raf V600 (BRAFV600) mutated tumors who have received prior BRAF inhibitor therapy either alone or in combination with MEK inhibitor as their only prior systemic therapy are eligible.
Patients must not have been treated with any of the following prior to Step 1 Randomization:\r\n* Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR\r\n* BRAF inhibitor including, but not limited to, vemurafenib or dabrafenib; regorafenib is not considered a BRAF inhibitor for the purpose of determining trial eligibility\r\n* Mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitor including, but not limited to, trametinib or selumetinib
Prior cytotoxic therapy and immunotherapy are allowed; for the dose escalation, prior targeted therapy with a MEK inhibitor, protein kinase C inhibitor, Akt, or mTOR inhibitor are allowed; for the dose expansion cohort, no prior MEK, protein kinase C (PKC), Akt, or mTOR inhibitors are allowed, and registration is limited to 10 total patients; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy; lesions treated with local or regional modalities such as radiofrequency ablation, or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging studies
Prior treatment with a mitogen-activated protein kinase kinase (MEK) inhibitor of any kind
History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment
Prior treatment with a Mitogen-Activated protein Kinase (MEK) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable).
Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor
Group 5: Patients with MEK mutated cancer
Prior therapy with a MEK- inhibitor
Prior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
Prior treatment with a selective inhibitor of RAF or MEK
Prior treatment with a BRAF inhibitor (including but not limited to dabrafenib [GSK2118436], vemurafenib, and LX281/BMS-908662) or a MEK inhibitor (including but not limited to trametinib [GSK1120212], AZD6244, and RDEA119); NOTE: there is no limit to the number of other prior therapies, and patients may be previously untreated
Patients previously treated with potent BRAF inhibitor or MEK inhibitor, including PLX4032/vemurafenib, ARQ 736 for more than 10 days; previous treatment with sorafenib is permitted
Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) prior to start of study treatment (Note: Prior treatment with dabrafenib is allowed for crossover subjects in Cohort A);
Prior MEK inhibitor therapy is allowed
Patients who have received prior treatment with a MEK inhibitor
Prior therapy with a mitogen-activated protein kinase kinase (MEK)-inhibitor
Prior therapy with a MEK inhibitor
Patients who have had prior VEGF pathway inhibitor, BRAF or MEK inhibitor therapy are ineligible.
History of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatment
Prior therapy with a MEK- inhibitor
Prior treatment with a BRAF inhibitor or MEK inhibitor
History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatment
Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
The subject has been previously treated with a Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor.
Prior treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, and XL281/BMS-908662) or a MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) or ipilimumab or any other agent targeting a T-cell immunomodulatory pathway (including, but not limited to CTLA-4, PD-1, 4-1BB, OX40, GITR, CD27, and CD28)
Prior therapy with a MEK inhibitor.
Part 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a mitogen-activated protein kinase (MEK) inhibitor (exception: prior treatment with sorafenib is permitted).
Prior treatment with selumetinib or another specific mitogen-activated protein kinase (MEK)1/2 inhibitor (unless the subject meets criteria for re-treatment)
Subjects who have not yet initiated but plan to undergo dosing with a tyrosine kinase inhibitor (TKI) or Raf inhibitor, either alone or with a MEK inhibitor, for treatment of metastatic melanoma, colon cancer, hepatic cell carcinoma, or thyroid cancer
History of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatment
Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitor