Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Atezolizumab

Immunoglobulins

Immunologic Factors

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants will receive atezolizumab monotherapy 1200 milligrams (mg) intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Participants will receive cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody

Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Cobimetinib

Regorafenib

Clinical Trials

This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.

A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)

A Phase III, Open-Label, Multicenter, Three-Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy vs. Regorafenib in Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Adenocarcinoma

Overall survival is defined as the time (in months) between the date of randomization and the date of death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Objective response and its 95% CI were calculated using the Clopper-Pearson method.

DOR is defined as the period measured from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. Median DOR was estimated using the Kaplan-Meier method, and the 95% CI was calculated using the method of Brookmeyer and Crowley.

The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.

Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infusion on Day 1 of Cycles 1 and 4; pre-infusion (0 hours) on Day 1 of Cycle 8 and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)

Hoffmann-La Roche

ITT was monitored for All-Cause Mortality, the safety analysis set (SAF) was assessed for Serious Adverse Events and Other (Not Including Serious) Adverse Events. SAF included all enrolled participants who received at least one dose of any study medication.

Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Cobimetinib + Atezolizumab

Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Communications

Analysis was performed on the ITT population.

Overall Survival (OS)

Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Analysis was performed on evaluable participants in the ITT population with measurable disease at baseline, as determined by the investigator.

Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1

DOR was assessed in participants who had an objective response during the study.

Duration of Response (DOR) According to RECIST Version 1.1

Week 3

Week 4

Week 6

Week 8

Week 9

Week 12

Week 15

Week 16

Week 18

Week 20

Week 21

Week 24

Week 27

Week 28

Week 30

Week 32

Week 33

Week 36

Week 39

Week 40

Week 42

Week 44

Week 45

Week 48

Week 51

Week 52

Week 54

Week 56

Week 57

Week 60

Week 64

Week 68

Treatment Discontinuation

Long Term Follow Up Month 3

Long Term Follow Up Month 6

Long Term Follow Up Month 30

Long Term Follow Up Month 33

Long Term Follow Up Month 36

Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score

Long Term Follow-up Month 3

Long Term Follow-up Month 6

Long Term Follow-up Month 30

Long Term Follow-up Month 33

Long Term Follow-up Month 36

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study

Serious AEs

Non-serious AEs

Analysis was performed on the SAF population.

Percentage of Participants With Adverse Events (AEs)

Cycle 1 Day 15 - Predose

Cycle 1 Day 15 - Postdose

Cycle 4 Day 15 - Predose

Cycle 4 Day 15 - Postdose

The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Only included participants in the Cobimetnib arm

Plasma Concentration of Cobimetinib

Cycle 1 Day 1 - Predose

Cycle 1 Day 1 - 30 min post dose

Cycle 2 Day 1 - Predose

Cycle 2 Day 1 - 30 min post dose

Cycle 3 Day 1 - Predose

Cycle 4 Day 1 - Predose

Cycle 4 Day 1 - 30 min post dose

Cycle 5 Day 1 - Predose

Cycle 5 Day 1 - 30 min post dose

Cycle 8 Day 1 - Predose

Cycle 16 Day 1 - Predose

Unscheduled

The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Also, only included participants to whom Atezolizumab was administered.

Serum Concentration of Atezolizumab

Analysis was performed on the SAF population and included participants with at least one predose and one postdose ATA assessment.

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Overall Study

Spots Global Cancer Trial Database for locally advanced or metastatic colorectal adenocarcinoma