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

Description

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).

Conditions

Advanced or Metastatic NRAS-mutant Melanoma

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Study Overview

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Study Details

Study overview

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).

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]

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

Condition
Advanced or Metastatic NRAS-mutant Melanoma
Intervention / Treatment

-

Contacts and Locations

San Francisco

University of California, San Francisco, San Francisco, California, United States, 94143

Englewood

The Melanoma and Skin Care Institute, Englewood, Colorado, United States, 80113

Miami

University of Miami Sylvester Cancer, Miami, Florida, United States, 33136

Kansas City

University of Kansas Cancer Center, Kansas City, Kansas, United States, 66205

Detroit

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, United States, 48201

Saint Louis

Washington University School of Medicine, Saint Louis, Missouri, United States, 63110

New York

Memorial Sloan Kettering Cancer Center, New York, New York, United States, 10065

Cleveland

Cleveland Clinic Foundation, Cleveland, Ohio, United States, 44195

Nashville

SCRI Oncology Partners (formerly Tennessee Oncology), Nashville, Tennessee, United States, 37203

Austin

Texas Oncology- Austin Midtown, Austin, Texas, United States, 78705

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Willing and able to provide written informed consent
  • 2. Age ≥ 18 years
  • 3. Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 7. ECOG performance status 0, 1 or 2
  • 8. Presence of at least 1 measurable lesion according to RECIST v1.1
  • 9. Able to swallow oral medication.
  • 1. Patients with uveal or mucosal melanoma
  • 2. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
  • 3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug(s) (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  • 4. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome)
  • 5. LVEF \<50%
  • 6. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
  • 7. Patients receiving treatment with herbal medicine known to cause liver toxicity, which cannot be discontinued 7 days prior to first dose of study drug(s) and for the duration of the study.
  • 8. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Ages Eligible for Study

18 Years to 99 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Erasca, Inc.,

Joyce Antal, STUDY_DIRECTOR, Clinical Development

Study Record Dates

2028-12