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

Launched by ERASCA, INC. · Mar 28, 2024

Keywords

ClinConnect Summary

The SEACRAFT-2 clinical trial is studying a combination of two medications, naporafenib and trametinib, for patients with a specific type of skin cancer called NRAS-mutant melanoma that has advanced or spread to other parts of the body. The trial has two stages. In the first stage, researchers will find the best dose of these medications to use. In the second stage, they will compare how long patients live without their cancer worsening (called progression-free survival) and overall survival between those receiving the combination treatment and those receiving other standard treatments chosen by their doctors.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of advanced NRAS-mutant melanoma that cannot be surgically removed. They should have already received treatment with a specific type of therapy known as anti-PD-1/L1 and have experienced disease progression. Participants will need to provide consent and have tumors that can be measured. This trial is currently recruiting patients, and it is important to note that individuals with certain other types of melanoma or prior treatments with specific drugs may not qualify. If enrolled, participants can expect regular monitoring and support throughout the study.

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Eligibility criteria

• Key Inclusion 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.
• Key Exclusion Criteria:
• • 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