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MAPK pathway inhibitors
Naporafenib + Trametinib for Melanoma
Phase 3
Recruiting
Research Sponsored by Erasca, Inc.
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial Must have
Age ≥ 18 years
ECOG performance status 0, 1 or 2
Must not have
Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
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)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up assessed up to 24 months from time of first dose
Awards & highlights
No Placebo-Only Group
Pivotal Trial
Summary
This trial aims to find the best dose of naporafenib + trametinib for Stage 1 and then compare the survival outcomes of patients with NRAS-mutant melanoma who receive
Who is the study for?
This trial is for adults over 18 with unresectable or metastatic cutaneous melanoma, including acral type, that has an NRAS mutation. Participants must have progressed on anti-PD-1/L1 therapy within the last 6 months and be able to take oral medication. They need at least one measurable lesion and a performance status of 0, 1, or 2.
What is being tested?
The study is in two stages: first to find the best dose of naporafenib plus trametinib; second to see if this combo improves survival compared to standard treatments (dacarbazine, temozolomide, or just trametinib) in patients with NRAS-mutant melanoma.
What are the potential side effects?
Potential side effects may include those common to cancer therapies such as fatigue, nausea, skin rash, liver function changes and other organ-related issues. Specific side effects related to Naporafenib and Trametinib will be monitored.
Eligibility Criteria
Inclusion Criteria
You may be eligible if you check “Yes” for the criteria belowSelect...
I am 18 years old or older.
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I can care for myself and am up and about more than 50% of my waking hours.
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My melanoma cannot be removed by surgery and may have spread.
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My cancer has an NRAS mutation confirmed by a certified lab test.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
I have been treated with drugs targeting ERK, MEK, RAF, or RAS.
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I do not have severe GI issues that could affect medication absorption.
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My heart's pumping ability is below normal.
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My melanoma is either in the eye (uveal) or in mucosal areas.
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I have or am at risk for a blocked vein in my eye due to conditions like uncontrolled glaucoma.
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My brain metastases are stable and not causing symptoms.
Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ assessed up to 24 months from time of first dose
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~assessed up to 24 months from time of first dose
Treatment Details
Study Objectives
Study objectives can provide a clearer picture of what you can expect from a treatment.Primary study objectives
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Stage 2: To compare PFS and OS for patients who are randomized to receive the combination of naporafenib + trametinib to that of patients who receive physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy)
Secondary study objectives
Adverse Events
Area under the curve (AUC):Stage 1 only
Disease Control Rate (DCR)
+5 moreOther study objectives
Disease Control Rate (DCR) for CNS disease in participants
Duration of Response (DOR) for CNS disease in participants
Overall Response Rate (ORR) for CNS disease in participants
Awards & Highlights
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.
Trial Design
5Treatment groups
Experimental Treatment
Active Control
Group I: Stage 2 Arm AExperimental Treatment2 Interventions
Naporafenib + Trametinib Naporafenib (ERAS-254) BID oral administration with Trametinib QD at the dose selected in Stage 1
Group II: Stage 1 Dose selection Lead-in Arm 2Experimental Treatment2 Interventions
Naporafenib + Trametinib Naporafenib (ERAS-254) 400 mg administered orally twice daily (BID) Trametinib 0.5 mg once daily (QD)
Group III: Stage 1 Dose selection Lead-in Arm 1Experimental Treatment2 Interventions
Naporafenib + Trametinib Naporafenib (ERAS-254) 100 mg administered orally twice daily (BID) Trametinib 1 mg once daily (QD)
Group IV: Stage 2 Arm B - Physician's ChoiceActive Control3 Interventions
* 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
Group V: Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapyActive Control1 Intervention
Trametinib 2 mg once daily (QD)
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Trametinib
2014
Completed Phase 2
~1550
Find a Location
Who is running the clinical trial?
Erasca, Inc.Lead Sponsor
7 Previous Clinical Trials
693 Total Patients Enrolled
Joyce AntalStudy DirectorClinical Development
2 Previous Clinical Trials
126 Total Patients Enrolled
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