Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Vemurafenib

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

Will be administered as per the schedule described in individual arm.

Atezolizumab Placebo

Cobimetinib

Vemurafenib Placebo

Clinical Trials

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.

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

PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first

PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first

Objective response is defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1

DOR, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first

OS is defined as the time from randomization to death from any cause

2-year landmark survival, defined as survival at 2 years

Time to deterioration in global health status/healthrelated quality of life (GHS/HRQoL), defined as the time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment.

The score range for each EORTC QLQ-C30 scale is from 0 to 100, with higher scores indicating better functioning and better GHS/HRQoL.

Time to deterioration in physical functioning, defined as the time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed physical functioning scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment.

The score range for each EORTC QLQ-C30 scale is from 0 to 100, with higher scores indicating better functioning and better GHS/HRQoL.

Presence of ADAs against atezolizumab during the study relative to the presence of ADAs at baseline

Hoffmann-La Roche

22 participants in the atezo+cobi+vem arm stopped treatment during the run-in period and received no atezo and 4 more in the atezo+cobi+vem arm completed the run-in period but did not receive atezolizumab. These 26 participants were included in the placebo+cobi+vem arm for safety evaluation. 3 participants from the placebo+cobi+vem arm were not treated with either cobimetinib or vemurafenib.

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 only 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.

Atezolizumab Placebo + Cobimetinib + Vemurafenib

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 only 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.

Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Communications

Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Progression-Free Survival (PFS), as Determined by Independent Review Committee Using RECIST v1.1

Responders

Non-Responders

ITT Population with measurable disease at baseline

Percentage of Participants With Objective Response, as Determined by Investigator Using RECIST v1.1

Duration of Response, as Determined by Investigator Using RECIST v1.1

Overall Survival

Percentage of Participants Who Have Survived at 2 Years

Time to Deterioration in Global Health Status Using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Scale Score

Time to Deterioration in Physical Functioning Using EORTC QLQ-C30 Physical Functioning Scale Score

Percentage of Participants With Adverse Events and Serious Adverse Events

Cycle 1 Day 1/30 Min Postdose

Cycle 2 Day 1/Predose

Cycle 3 Day 1/Predose

Cycle 4 Day 1/Predose

Cycle 4 Day 1/30 Min Postdose

Study Drugs Discontinuation Visit

Serum Concentration of Atezolizumab

Cycle 1 Day 15/Predose

Cycle 1 Day 15/3-6 Hr Postdose

Cycle 4 Day 15/Predose

Cycle 4 Day 15/3-6 Hr Postdose

The PK-evaluable population is defined as all participants who have received any dose of Cobimetinib 20/40 mg and for whom at least one evaluable PK sample is collected.

Plasma Concentration of Cobimetinib Dose: 20/40 mg

The PK-evaluable population is defined as all participants who have received any dose of Cobimetinib 60 mg and for whom at least one evaluable PK sample is collected.

Plasma Concentration of Cobimetinib Dose: 60 mg

Cycle 1 Day 15/ predose

Cycle 1 Day 15/ 3-6 hr

Cycle 4 Day 15/ predose

Cycle 4 Day 15/ 3-6 hr postdose

Vemurafenib PK was characterized in the PK-evaluable population, of 218 out of 255 treated in the placebo+cobi+vem arm and 209 out of 256 treated in the atezo+cobi+vem arm.

Plasma Concentration of Vemurafenib

Baseline evaluable participants

Post-baseline evaluable participants

The ADA-evaluable population was defined as participants who received at least one dose of Atezolizumab and had ≥ 1 post-baseline ADA result.

Percentage of Participants Positive for Anti-Drug Antibodies (ADA) to Atezolizumab

Overall Study

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m\^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Paclitaxel will be administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 \[PD-L1\] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40 months). In addition, the Sponsor may decide to terminate the study at any time.

The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.

A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

A Phase III, Multicenter, Randomised, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-Pd-L1 Antibody) in Combination With Paclitaxel Compared With Placebo With Paclitaxel for Patients With Previously Untreated Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer

PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

OS is defined as the time from randomization to death from any cause. Results from a pre-specified interim analysis.

Deterioration in Global Health Status/HRQoL is defined as a decrease of at least 10 points on the Global Health Status /HRQoL scale (comprised of 2 items: 29 and 30) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The 2 items use 7-point scale (1 = very poor to 7 = Excellent). Scores are averaged, transformed to 0-100 scale; where higher score=better level of functioning or greater degree of symptoms.

PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.

Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD.

DOR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to \<10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

Clinical benefit is defined as the achievement of CR, PR, or stable disease according to RECIST v1.1 that lasts for at least 6 months. CR is defined as the disappearance of all TLs and SA reduction to \<10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference smallest SD since treatment started.

Investigator text for AEs is coded using MedDRA version 25.1

C-DoR is defined as the time from the first occurrence of a documented confirmed response (CR or PR) in C-DOR evaluable population until the date of disease progression per RECIST v1.1 or death from any cause, whichever occurs first. Responses were confirmed after 8 weeks if within first 12 months or after 12 weeks if later.

Atezolizumab + Paclitaxel

Placebo + Paclitaxel

Placebo and Paclitaxel

Atezolizumab and Paclitaxel

PD-L1-positive subpopulation: participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization

Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Subpopulation With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status

ITT population: all randomized participants, whether or not the assigned study treatment was received

Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

Overall Survival (OS) in the PD-L1-Positive Subpopulation

Overall Survival (OS) in the ITT Population

12 months

18 months

Percentage of Participants Who Are Alive at 12 and 18 Months

PRO-evaluable populations: participants in the ITT population with baseline PRO assessment and at least one post-baseline PRO assessment in the questionnaire of interest (European Organization for the Research and Treatment of Cancer \[EORTC\] Quality-of-life Questionnaire \[QLQ\] C30, EORTC QLQ BR-23 or FACT-G)

Time to Deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) in the PRO Evaluable Population

Percentage of Participants Who Are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Confirmed, Investigator-Assessed )

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the PD-L1-Positive Population (Unconfirmed, Investigator-Assessed)

Response-evaluable population: participants in the ITT population with measurable disease at baseline

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Confirmed, Investigator-Assessed )

Percentage of Participants With Objective Response Assessed Using RECIST v1.1 in the Response-Evaluable Population (Unconfirmed, Investigator-Assessed )

Duration of response (DoR)-evaluable population: participants in the ITT population with measurable disease at baseline

Duration of Objective Response (DOR) Assessed Using RECIST v1.1 in DOR-evaluable Population (Unconfirmed)

Clinical Benefit Rate analysis included all participants with unconfirmed PR/CR or SD of at least 6 months duration

Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 in Response-evaluable Population

C2D1 predose

C3D1 predose

C4D1 predose

PK-evaluable population: all participants who received any dose of Atezolizumab and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in PK Evaluable Population

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in PK-evaluable Population

PK-evaluable population: first 60 participants who received any dose of Paclitaxel and who have at least one evaluable post-baseline PK sample. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Minimum Observed Plasma Concentration (Cmin) of Paclitaxel

C1D1 Post-Dose

C3D1 Post-Dose

Maximum Observed Plasma Concentration (Cmax) of Paclitaxel

Percentage of participants with at least one AE

Percentage of participants with at least one SAE

Safety-evaluable population: participants who received any amount of any study drug. For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

Percentage of participants positive for ADA at Baseline

Percentage of participants positive for ADA Post-baseline

Anti-Drug Antibody (ADA) population:

* Baseline ADA-evaluable population: all participants with at least one evaluable ADA assay result from a baseline sample
* Post baseline ADA-Evaluable population: all participants with at least one evaluable ADA assay result from at least one post-baseline sample.

For all safety, PK and immunogenicity analyses, participants were grouped according to the treatment actually received, including cases in which atezolizumab was received in error.

Percentage of Participants With Anti-Drug Antibodies' (ADAs) Against Atezolizumab in ADA Evaluable Population

PD-L1 IC0

PD-L1 IC1/2/3

Overall Survival by PD-L1 Status, Intent to Treat Population

Progression Free Survival by PD-L1 Status, Intent to Treat Population

Duration of confirmed response (C-DoR)-evaluable population: participants in the ITT population with measurable disease at baseline and with a confirmed objective response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT02908672	Melanoma	Atezolizumab Atezolizumab Pl... Cobimetinib Vemurafenib Vemurafenib Pla...	18 Years -	Hoffmann-La Roche
A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)	NCT03125902	Triple-Negative...	Atezolizumab (M... Atezolizumab Pl... Paclitaxel	18 Years -	Hoffmann-La Roche
A Study of Atezolizumab Versus Placebo in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Participants With Newly-Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT03038100	Ovarian Cancer Fallopian Tube ... Peritoneal Neop...	Paclitaxel Carboplatin Atezolizumab Bevacizumab Atezolizumab Pl...	18 Years -	Hoffmann-La Roche
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	NCT02908672	Melanoma	Atezolizumab Atezolizumab Pl... Cobimetinib Vemurafenib Vemurafenib Pla...	18 Years -	Hoffmann-La Roche

Spots Global Cancer Trial Database for atezolizumab placebo