Phase II Biomarker Study Comparing the Combination of BRAF Inhibitor Dabrafenib With MEK Inhibitor Trametinib Versus the Combination After Monotherapy With Dabrafenib or Trametinib

Inclusion Criteria:

* Participant with signed written informed consent;
* Participants of age \>=18 years;
* Participants with histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) (according to American Joint Committee on Cancer \[AJCC\] staging 7th edition).
* BRAF (proto-oncogene B-Raf) V600E/K mutation-positive confirmed by a local laboratory.
* Accessible melanoma tumours for biopsies (locally advanced primary melanoma or metastases)
* Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) on not biopsied lesions.
* All prior anti-cancer treatment-related toxicities (except alopecia) must be \<= Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0) at the time of randomisation.
* Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomisation and agree to use effective contraception, throughout the treatment period, and for 4 months after the last dose of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
* Adequate baseline organ function as defined : absolute neutrophil count \>= 1.2 × 109/Liters (L); Haemoglobin \>= 9 grams(g)/Deciliter (dL); Platelet count \>= 75 x 109/L; prothrombin time(PT)/ international normalized ratio (INR) and partial thromboplastin time (PTT) \<= 1.5 x Upper limit of normal (ULN); Albumin \>= 2.5 g/dL; Total bilirubin- \<= 1.5 x ULN; aspartate aminotransferase(AST) and alanine transaminase (ALT) \<= 2.5 x ULN; Calculated creatinine clearance \>=50 mL/min; Left Ventricular Ejection fraction (LVEF) \>= Lower limit of normal (LLN) by Echocardiogram (ECHO)

Exclusion Criteria:

* Prior treatment with a BRAF or MEK inhibitor
* Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomisation and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomisation.
* Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to randomisation
* Current use of a prohibited medication.
* Refusal of tumour and skin biopsies.
* History of another malignancy.
* Any serious and/or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the participant's safety, obtaining informed consent, or compliance with study procedures.
* Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed).
* A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
* Brain metastases are excluded unless: All known lesions were previously treated with surgery or stereotactic surgery (whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery), OR Brain lesion(s), if still present, must be confirmed stable (i.e., no increase in lesion size) for \>= 12 weeks prior to randomisation (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast, AND Asymptomatic with no corticosteroid requirements for \>= 4 weeks prior to randomisation, AND No enzyme inducing anticonvulsants for \>= 4 weeks prior to randomisation.
* A history or evidence of cardiovascular risk including any of the following: LVEF \< LLN; A QT interval corrected for heart rate using the Bazett's formula (QTcB) \>= 480 milliseconds (msec); A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Participants with atrial fibrillation controlled for \> 30 days prior to randomisation are eligible; A history (within 6 months prior to randomisation) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty; A history or evidence of current \>= Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic \> 140 millimetres of mercury (mmHg) and/or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy; Participants with intra-cardiac defibrillators or permanent pacemakers; Known cardiac metastases; Abnormal cardiac valve morphology (\>=grade 2) documented by echocardiogram (Participants with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study). Participants with moderate valvular thickening should not be entered on study.
* A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including: Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping; Evidence of new visual field defects on automated perimetry; Intraocular pressure \>21 mmHg as measured by tonography.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
* Pregnant or lactating females
* Interstitial lung disease or pneumonitis