A Study of RO5212054 (PLX3603) in Patients With BRAF V600-mutated Advanced Solid Tumours

• Dose-escalation phase: Safety and tolerability, dose-limiting toxicities, maximum tolerated dose (adverse events, ECG, vital signs, dermatological evaluation, haematology, serum chemistry, urinalysis) [ Time Frame: from baseline to 28 days after last dose of study drug ] [ Designated as safety issue: No ]
• Pharmacokinetics: Cmax, Tmax, AUC, elimination [ Time Frame: from baseline to 28 days after last dose of stdy drug ] [ Designated as safety issue: No ]
• Extension cohort: Tumour response according to RECIST criteria (best overall response rate, duration of response, progression-free survival) assessed by CT or MRI [ Time Frame: from baseline to disease progression ] [ Designated as safety issue: No ]

• Overall safety profile: Adverse events, ECG, vital signs, dermatological evaluation, haematology, serum chemistry, urinalysis [ Time Frame: through to end of study ] [ Designated as safety issue: No ]
• Dose-escalating phase: Preliminary evidence of anti-tumour activity according to RECIST criteria, tumour assessments by CT/MRI [ Time Frame: from baseline to disease progression ] [ Designated as safety issue: No ]
• Pharmacodynamic impact on mitogen activated protein kinase (MAPK) inhibition, assessed by tumour biopsy [ Time Frame: from baseline to disease progression ] [ Designated as safety issue: No ]

This open-label, multi-center study will evaluate the safety, tolerability, pharmacokinetics and efficacy of RO5212054 [PLX3603] in patients with BRAF V600-mutated advanced solid tumours. Cohorts of patients will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• adult patients, >/= 18 years of age
• advanced solid tumour
• dose-escalation phase: either relapsed/refractory disease after prior therapy or melanoma patients with newly diagnosed (treatment-naïve) unresectable AJCC stage IIIC or stage IV disease are eligible
• melanoma extension phase: newly diagnosed unresectable AJCC stage IIIC or IV disease
• colorectal cancer extension phase: relapsed/refractory metastatic disease
• confirmed BRAF V600 mutation status; for extension phases confirmation by Cobas test required
• ECOG performance status 0-1
• adequate liver, renal and bone marrow function

Exclusion Criteria:

• patients for whom standard therapy exists and is considered appropriate by the investigator
• for melanoma patients in the extension phase: prior systemic therapy for advanced disease (prior adjuvant immunotherapy allowed)
• prior treatment with an inhibitor of BRAF (sorafenib allowed)
• active CNS lesions, or history of or known carcinomatous meningitis
• treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
• anticipated or ongoing anti-cancer therapies other than those administered in this study
• serious cardiovascular illness within the 6 months prior to study drug administration