SEACRAFT-2

• Research type

  Research Study

• Full title

  A randomized, open-label Phase 3 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]

• IRAS ID

  1009792

• Contact name

  Travis Suttle

• Contact email

  tsuttle@erasca.com

• Sponsor organisation

  Erasca, Inc.

• Eudract number

  2024-511404-17

• Clinicaltrials.gov Identifier

  NCT06346067

• Research summary

  This study (SEACRAFT-2) is designed 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 melanoma with metastatic neuroblastoma rat sarcoma mutantion (NRASm) which cannot be removed with surgery who have progressed on, or are intolerant to, standard of care therapy.
  This is a study which will be conducted on a large number of patients for whom the drug is intended. It is an open-label study, which means that both the subjects and the investigators will have knowledge of the assigned treatment. A total of up to approximately 470 eligible patients will be randomized to receive study drug(s) in this study across 2 stages.
  Male and female adult (age ≥18 years) patients with confirmed Stage III or Stage IV skin melanoma which cannot be removed with surgery and not reacting to local therapy are eligible to participate.

  The study participants will receive one of the following during Stage 1 of the study:
  1. Naporafenib 100 mg by mouth, twice daily, administered with trametinib 1 mg by mouth once daily
  2. Naporafenib 400 mg by mouth, twice daily, administered with trametinib 0.5 mg by mouth once daily
  3. Trametinib single drug therapy, 2 mg by mouth once daily

  During Stage 2 of the study, participants will receive one of the following:
  1. Naporafenib twice daily administered with trametinib once daily at the dose selected in Stage 1.
  2. 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 by mouth once daily

• REC name

  London - Hampstead Research Ethics Committee

• REC reference

  24/LO/0463

• Date of REC Opinion

  5 Aug 2024

• REC opinion

  Further Information Favourable Opinion