Advanced or Metastatic Melanoma
Conditions
Keywords
NRAS-Mutant, Melanoma
Brief summary
This is a Phase 2 open-label, multicenter, single-arm study evaluating the combination of Belvarafenib and Cobimetinib in patients with locally advanced or metastatic melanoma with NRAS mutations. The study plans to assess ORR, DCR, DOR, TTP, PFS, OS and safety of the participating subjects. Treatment cycles for all subjects will be 28 days in duration and Belvarafenib and Cobimetinib will be administered orally in combination.
Interventions
DRUGBelvarafenib
Belvarafenib will be taken twice daily (BID) on Days 1-28 of each cycle
COMBINATION_PRODUCTCobimetinib
Cobimetinib will be taken on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of each cycle (three times weekly, TIW), followed by a drug holiday through Day 28
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have histologically, cytologically confirmed locally advanced or metastatic melanoma for which no adequate standard of care exists, or for which standard of care has failed or is not tolerated. * Have NRAS mutation. * Have at least one measurable lesion at baseline per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * Age of 19 years or older * Adequate renal, hematologic and liver function. Key
Exclusion criteria
* Have a history of prior treatment with RAF, MEK, or ERK inhibitor. * Have past history or ongoing retinal pathology that is considered a risk factor for retinopathy or RVO. * Have past history or ongoing cardiac function-related disorders. * Had hemorrhage or bleeding corresponding to CTCAE Grade ≥3 within 4 weeks prior to the first dose of study drug treatment (Cycle 1 Day 1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years) | ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Independent Central Review (ICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years) | DCR will be measured as the proportion of subject with confirmed CR, PR, or Stable Disease (SD) as per RECIST v1.1 by Independent Central Review (ICR) |
| Duration of response (DOR) | Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years) | DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v1.1 by Independent Central Review (ICR) or death from any cause, whichever occurs first. |
| Progression-free survival (PFS) | Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years) | PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v1.1 by Independent Central Review (ICR) or until death from any cause, whichever occurs first |
| Time to progression (TTP) | Throughout the study until disease progression (up to approximately 3 years) | TTI will be measured from date of first treatment until date of rediographic progression as per RECIST v1.1 by Independent Central Review (ICR) |
| Overall survival (OS) | Throughout the study until the date of death (up to approximately 3 years) | OS will be measured from the first administration of the study drug to the date of death due to any cause |
Countries
South Korea
Contacts
CONTACTYoung Su (Bobby) Noh
Outcome results
None listed