Your Health, We Care
The safety and efficacy of cobimetinib were established in a multicenter, randomized (1:1), double-blind, placebo-controlled trial. This trial enrolled 495 patients with previously untreated, BRAF V600 mutation-positive, unresectable or metastatic melanoma. The presence of BRAF V600 mutations was detected using the cobas® 4800 BRAF V600 Mutation Test.
All patients received vemurafenib 960 mg orally twice daily on Days 1–28. They were randomly assigned to additionally receive either cobimetinib 60 mg or matching placebo orally once daily on Days 1–21 of each 28-day cycle. Randomization was stratified by geographic region (North America vs. Europe vs. Australia/New Zealand/Others) and disease stage (unresectable Stage IIIc, Stage M1a, or Stage M1b vs. Stage M1c). Treatment continued until disease progression or the occurrence of unacceptable toxicity. Patients randomly assigned to the placebo group did not receive cobimetinib upon disease progression.
Primary and Secondary Efficacy Outcomes
The primary efficacy outcome was progression-free survival (PFS) as assessed by investigators per RECIST v1.1 criteria. Other efficacy outcomes included:
Confirmed objective response rate (ORR) as assessed by investigators;
Overall survival (OS);
Progression-free survival (PFS) as assessed by a blinded independent central review;
Duration of response (DOR).
Study Population Characteristics
The median age of the study population was 55 years (range: 23–88 years). Among the patients:
58% were male;
93% were White, and 5% had no reported race;
60% had Stage M1c disease;
72% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 at baseline;
45% had elevated serum lactate dehydrogenase (LDH) at baseline;
10% had previously received adjuvant therapy;
<1% had previously treated brain metastases.
Next-generation sequencing (NGS) was used for retrospective testing of available tumor samples to further classify mutations as V600E or V600K. Test results were obtained for 81% of randomly assigned patients, of whom 86% were identified as having the V600E mutation and 14% as having the V600K mutation.
Notes on Key Terms
"RECIST v1.1" (Response Evaluation Criteria in Solid Tumors Version 1.1): The international standard for assessing solid tumor treatment response, retained in its original abbreviation for medical accuracy.
"ECOG performance status": A widely used scale for evaluating a patient’s ability to perform daily activities, full name "Eastern Cooperative Oncology Group performance status" is added for clarity.
"cobas® 4800 BRAF V600 Mutation Test": A commercialized in vitro diagnostic test, with its brand name and full product name retained to conform to clinical trial documentation standards.
FDA，2023.05
