NCT02908672|CompletedPhase 3Results

A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma

A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma

Hoffmann-La Roche ClinicalTrials.gov

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2 other identifiers

CO392622016-002482-54

Study Type

interventional

Target

514

Locations

19 countries

Sites

106

Timeline

RegisteredSep 2016

StartedJan 2017

CompletionJul 2024

Brief Summary

This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

514

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Jan 2017

Longer than P75 for phase_3

Geographic Reach

19 countries

106 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.5 years study duration

First Submitted

Initial submission to the registry

September 19, 2016

Completed

2 days until next milestone

First Posted

Study publicly available on registry

September 21, 2016

Completed

4 months until next milestone

Study Start

First participant enrolled

January 13, 2017

Completed

2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 11, 2019

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

November 19, 2020

Completed

3.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2024

Completed

Last Updated

July 20, 2025

Status Verified

June 1, 2025

Enrollment Period

2.7 years

First QC Date

September 19, 2016

Results QC Date

September 15, 2020

Last Update Submit

June 26, 2025

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

Secondary Outcomes (13)

PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)
Percentage of Participants With Objective Response (OR), as Determined by Investigator Using RECIST V1.1
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)
Duration of Response (DOR), as Determined by Investigator Using RECIST v1.1
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)
Overall Survival (OS)
Baseline up to death due to any cause (up to approximately 85 months)
Percentage of Participants Who Have Survived at 2 Years
2 years
+8 more secondary outcomes

Study Arms (2)

Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo

EXPERIMENTAL

Run-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive atezolizumab 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.

Drug: AtezolizumabDrug: CobimetinibDrug: VemurafenibDrug: Vemurafenib Placebo

Atezolizumab Placebo + Cobimetinib + Vemurafenib

EXPERIMENTAL

Run-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.

Drug: Atezolizumab PlaceboDrug: CobimetinibDrug: Vemurafenib