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Kinase Inhibitor

DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib for Melanoma

Phase 1

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months)

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This open-label, dose-escalation study of vemurafenib in combination with cobimetinib will evaluate the safety, tolerability and pharmacokinetics in participants with BRAFV600 mutation-positive metastatic melanoma. Participants with previously untreated, BRAFV600E mutation-positive, locally advanced/unresectable or metastatic melanoma or those who have progressed on vemurafenib monotherapy immediately prior to enrolling in this trial are eligible. Participants will be assigned to different cohorts with escalating oral doses of vemurafenib and cobimetinib. This study consists of 2 stages, Stage 1 (Dose Escalation Stage \[DES\] and Cohort Expansion Stage \[CES\]) and the anticipated time on study treatment is until disease progression, unacceptable toxicity or any other discontinuation criterion is met.

Eligible Conditions

Melanoma

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1

Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES

Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts

Secondary study objectives

Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2

Median Duration of Response (DOR)

Overall Survival (OS)

+3 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: DES (Cohort 4): 80 mg Cobimetinib + 960 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group II: DES (Cohort 3): 60 mg Cobimetinib + 960 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group III: DES (Cohort 2A): 100 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group IV: DES (Cohort 2): 80 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group V: DES (Cohort 1D): 60 mg Cobimetinib + 960 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group VI: DES (Cohort 1C): 60 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on Days 1-28 (28/0 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group VII: DES (Cohort 1B): 60 mg Cobimetinib + 960 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group VIII: DES (Cohort 1A): 60 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on Days 1-21, followed by 7 days off on Days 22-28 (21/7 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group IX: DES (Cohort 1): 60 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 milligrams (mg) cobimetinib once daily (QD) on Days 1-14, followed by 14 days off on Days 15-28 (14/14 dosing schedule) and oral 720 mg vemurafenib twice daily (BID) on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group X: Cobimetinib Monotherapy (100 mg or 60 mg)Experimental Treatment1 Intervention

Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Group XI: CES (Cohort 1B): 60 mg Cobimetinib + 960 mg VemurafenibExperimental Treatment2 Interventions

Group XII: CES (Cohort 1A): 60 mg Cobimetinib + 720 mg VemurafenibExperimental Treatment2 Interventions

Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vemurafenib

FDA approved

Cobimetinib

FDA approved

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