A Randomized, Open-label Phase III Study in Patients With Previously Treated Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma Comparing the Combination of Naporafenib + Trametinib to Physician's Choice of Therapy (Dacarbazine, Temozolomide or Trametinib Monotherapy) With a Dose Optimization lead-in [SEACRAFT-2]
Status: Recruiting
Location: See all (56) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY
Stage 1: To select the optimal dose of naporafenib + trametinib to be studied in Stage 2. Stage 2: To compare progression free survival (PFS) and overall survival (OS) for patients with NRAS-mutant (NRASm) melanoma who are randomized to receive the combination of naporafenib + trametinib to that of patients who are randomized to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy).
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 99
Healthy Volunteers: f
View:
• Willing and able to provide written informed consent
• Age ≥ 18 years
• Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma.
• Documentation of an NRAS mutation (tumor tissue or blood) prior to first dose of study drug(s) as determined locally with an analytically validated assay in a certified testing laboratory.
• Archival tumor tissue collected within 5 years prior to enrollment must be confirmed to be available at the time of Screening, which may be submitted before or after enrollment for exploratory biomarker analysis.
• Must have received an anti-PD-1/L1 based regimen (monotherapy or combination). Patient must have documented disease progression either while receiving therapy or within 12 weeks of last dose of the most recent anti-PD-1/L1 based regimen; the patient is eligible if they have received other therapies between the most recent anti-PD-1/L1 based regimen and enrollment.
• ECOG performance status 0, 1 or 2
• Presence of at least 1 measurable lesion according to RECIST v1.1
Active_comparator: Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy
Trametinib 2 mg once daily (QD)
Experimental: Stage 2 Arm A
Naporafenib + Trametinib Naporafenib (ERAS-254) BID oral administration with Trametinib QD at the dose selected in Stage 1
Active_comparator: Stage 2 Arm B - Physician's Choice
* Dacarbazine 1000 mg/m2 intravenously (IV) on Day 1 of each 21-day cycle OR~* Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle OR~* Trametinib monotherapy, 2 mg PO QD