A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022/KEYNOTE-022)

Inclusion criteria:

- Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic
(Stage IV) melanoma excluding mucosal, or ocular melanoma (or a histologically or
cytologically-documented locally-advanced or metastatic solid malignancy in Parts 4
and 5)

- At least 1 measurable lesion as defined by RECIST 1.1 on imaging studies (computed
tomography [CT] or magnetic resonance imaging [MRI])

- For solid tumors other than melanoma, (in Part 4 or 5 [dose confirmation only]),
participants must have a malignancy that is incurable and has either: (a) failed prior
standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is
not considered appropriate by the participants and treating physician. There is no
limit to the number of prior treatment regimens, but prior treatment(s) should not
include compounds targeting programmed cell death 1 (PD-1), PD-1 ligand 1 (PD-L1),
BRAF, or mitogen-activated protein kinase (MEK). Treatment must end at least 4 weeks
prior to randomization.

- BRAF mutation-positive (V600 E or K) melanoma for Parts 1, 2 and 3, or for Parts 1, 2,
4 and 5 only BRAF mutation-negative (wild type) melanoma with documented progression
of >=1 measurable lesion after prior therapy (if prior therapy was received). The
inclusion criterion does not apply to participants with solid tumors in Parts 4 and 5
(dose confirmation only).

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Anticipated life expectancy of at least 3 months

- Able to swallow and retain oral medication and no clinically significant
gastrointestinal abnormalities that may alter absorption such as malabsorption
syndrome or major resection of the stomach or bowels

- Adequate organ function

- Provide tissue for biomarker analysis from a newly or recently-obtained biopsy (within
90 days of Study Day 1) of a tumor lesion not previously irradiated

- Female participants of non-childbearing potential must be willing to use highly
effective contraceptive measures from the Screening Visit (Visit 1) through 120 days
after the last dose of study drug; male participants must agree to use an adequate
method of contraception starting with the first dose of study drug through 120 days
after the last dose of study drug

- Female participants of childbearing potential should have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study drug

Exclusion criteria:

- Currently participating in or has participated in a study of an investigational agent
or using an investigational device within 4 weeks of the first dose of study drug

- Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF
mutation-negative and has received >1 prior systemic therapy for metastatic melanoma

- Prior therapy with compounds targeting PD-1, PD-L1, BRAF, mitogen-activated protein
kinase (MEK) or other molecules in the mitogen-activated protein kinase (MAPK) pathway

- BRAF mutation-positive and has received prior systemic therapy with ipilimumab or
other anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibodies. The BRAF
exclusion criterion does not apply to participants with solid tumor in Parts 4 and 5
(dose confirmation only).

- Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the
first dose of study drug, or not recovered from clinically significant adverse events
due to cancer therapeutics administered more than 4 weeks prior to the first dose of
study drug

- Expected to require any other form of systemic or localized antineoplastic therapy
while in this study

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early stage cancers (carcinoma in situ or stage 1) treated with
curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially
curative therapy

- Active central nervous system (CNS) metastases and/or carcinomatous meningitis

- Active infection requiring systemic therapy

- Active autoimmune disease, or documented history of autoimmune disease, or a syndrome
that requires systemic steroids or immunosuppressive agents

- Previous severe hypersensitivity reaction to treatment with another monoclonal
antibody (mAb)

- On chronic systemic steroid therapy (>10 mg/day prednisone or equivalent) within 2
weeks prior to first dose of study drug or on any other form of immunosuppressive
medication

- History or evidence of cardiovascular risk

- Uncorrectable electrolyte abnormalities, long QT syndrome or taking medications known
to prolong the QT interval

- History of prior or current retinal vein occlusion (RVO)

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drugs, their excipients, and/or dimethyl sulfoxide
(DMSO)

- Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow
transplant

- History of (non-infectious) pneumonitis that required steroids or current pneumonitis

- Human immunodeficiency virus (HIV)

- Hepatitis B or C

- Received a live vaccine within 30 days prior to first dose of study drug

- Pregnant or breastfeeding or expecting to conceive or father children from the
Screening Visit (Visit 1) through 120 days after last dose of study drug