A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

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

Official Title
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An Open-Label, Multiple Ascending Dose (MAD) Study of the Selective BRAF Inhibitor RO5212054 (PLX3603) to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With BRAF V600-Mutated Advanced Solid Tumours

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: RO5212054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumor Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate liver, renal and bone marrow function Exclusion Criteria: Participants for whom standard therapy exists and is considered appropriate by the investigator Prior treatment with an inhibitor of BRAF (sorafenib allowed) Active Central nervous system (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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO5212054: Continuous Dosing Cohort<br>Participants will receive RO5212054 in escalating dose levels. | Drug: RO5212054<br>* Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned.<br>* Other names: PLX3603;|
| Experimental: RO5212054: New Formulation (F05) Bridging Cohort<br>Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort. | Drug: RO5212054<br>* Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned.<br>* Other names: PLX3603;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Dose Limiting Toxicity |  | Baseline up to 21 days | 
| Maximal Tolerated Dose of RO5212054 |  | Baseline up to 21 days | 
| Maximum Plasma Concentration of RO5212054 | Detailed timeframe: Pre-dose (0 hour [hr]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | 
| Time to Reach Maximum Plasma Concentration of RO5212054 | Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | 
| Area Under The Plasma Concentration-Time Curve of RO5212054 | Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | Baseline up to approximately 7 years |