Phase 1
N=155
Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT03178851 ↗Enrolled (actual)
155
Serious AEs
40.0%
Results posted
Jun 2020
Primary outcome: Primary: Investigator-Assessed Objective Response Rate (ORR) — 12.0; 36.4; 38.5 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Atezolizumab (Biological); Cobimetinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- May 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Investigator-Assessed Objective Response Rate (ORR) |
12.0; 36.4; 38.5 | — |
| PRIMARY Investigator-Assessed Disease Control Rate (DCR) |
37.0; 54.5; 46.2 | — |
| SECONDARY Investigator-Assessed Duration of Response (DOR) |
24.2; NA; NA | — |
| SECONDARY Overall Survival (OS) |
12.5; NA; 22.0 | — |
| SECONDARY Investigator-Assessed Progression-Free Survival (PFS) |
3.7; 9.3; 3.7 | — |
| SECONDARY Serum Concentration of Atezolizumab |
271; 275; 388; 65.3; 32.9; 73.2 | — |
| SECONDARY Plasma Concentration of Cobimetinib |
165; 125; 318; 208 | — |
| SECONDARY Percentage of Participants With Adverse Events |
98.9; 100; 100 | — |
| SECONDARY Change From Baseline in Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab |
32.5; 30.0; 10.0 | — |
| SECONDARY Cohort C: Independent-Review-Committee-Assessed (IRC) ORR |
27.3 | — |
| SECONDARY Cohort C: IRC-Assessed DCR |
38.6 | — |
| SECONDARY Cohort C: IRC-Assessed DOR |
NA | — |
| SECONDARY Cohort C: IRC-Assessed PFS |
3.7 | — |
Summary
This study will evaluate the preliminary efficacy, safety, and pharmacokinetics of cobimetinib and atezolizumab in participants with advanced BRAF V600-wild type (WT), metastatic, or unresectable locally advanced melanoma who have progressed on prior anti-PD-1 therapy. In addition, this study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab monotherapy in participants with BRAFV600-WT metastatic or unresectable locally advanced melanoma, who have not been previously treated.
Eligibility Criteria
Inclusion criteria
Disease-Specific Inclusion Criteria: Cohorts A and B:
- Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAF V600 WT (locally advanced) melanoma
- Documentation of BRAF V600 mutation-negative status in melanoma tumor tissue (archival [ /=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
- History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
- Anticipated use of any concomitant medication during or within 7 days before initiation of study treatment that is known to cause QT prolongation
- Any psychological, familial, sociological, or geographic condition that may hamper compliance with the protocol and follow-up after treatment discontinuation
- History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment
- Pregnant or breastfeeding, or intending to become pregnant during the study
- Known clinically significant liver disease
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk for treatment complications
- Treatment with a live, attenuated vaccine within 4 weeks before initiation of study treatment, or anticipation of need for such a vaccine during the course of the study
- Known hypersensitivity to any component of the atezolizumab or cobimetinib formulations
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent
- Inability or unwillingness to swallow pills
- Requirement for concomitant therapy or food that is prohibited during the study
Data sourced from ClinicalTrials.gov (NCT03178851). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.