NCT06346067

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)

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: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Erasca, Inc. · Industry
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

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).

Detailed description

SEACRAFT-2 is a global, Phase III, open-label, randomized study to assess the efficacy and safety of naporafenib administered with trametinib compared to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in patients with unresectable or metastatic NRAS mutant melanoma who have progressed on, or are intolerant to, an anti-programmed death-1 ligand 1 (PD 1/L1)-based regimen. The study will consist of 2 stages: dose optimization in Stage 1 and the Phase 3 portion in Stage 2. A total of approximately 470 eligible patients will be randomized to receive study drug(s) in this study across 2 stages.

Conditions

• Advanced or Metastatic NRAS-mutant Melanoma

Interventions

Type	Name	Description
DRUG	Naporafenib	Naporafenib (ERAS-254) is an experimental Pan-Raf inhibitor
DRUG	Dacarbazine	Dacarbazine IV - Day 1
DRUG	Temozolomide	Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle
DRUG	Trametinib	Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.

Timeline

• Start date: 2024-04-29
• Primary completion: 2028-04-01
• Completion: 2028-12-01
• First posted: 2024-04-03
• Last updated: 2026-02-27

Locations

59 sites across 9 countries: United States, Australia, Canada, Czechia, France, Italy, Netherlands, Spain, United Kingdom

Regulatory

• FDA-regulated drug study