A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
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).
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Willing and able to provide written informed consent
- Age ≥ 18 years
- Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma.
- 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.
- 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.
- 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.
- ECOG performance status 0, 1 or 2
- Presence of at least 1 measurable lesion according to RECIST v1.1
- Able to swallow oral medication.
Exclusion criteria
- Patients with uveal or mucosal melanoma
- 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)
- 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)
- LVEF <50%
- Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
- 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.
- Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06346067
Intervention or treatment
DRUG: Naporafenib
DRUG: Dacarbazine
DRUG: Temozolomide
DRUG: Trametinib
Conditions
- Advanced or Metastatic NRAS-mutant Melanoma
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Calvary Mater Newcastle
Select from list below to view details:
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Tasman Health Care
Southport, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Peter MacCallum Cancer Institute
Melbourne, Victoria, Australia
Loading map...
Who is running the clinical trial?
Erasca, Inc.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Stage 1 Dose selection Lead-in Arm 1
| Drug: Naporafenib, Drug: Trametinib |
EXPERIMENTAL: Stage 1 Dose selection Lead-in Arm 2
| Drug: Naporafenib, Drug: Trametinib |
ACTIVE_COMPARATOR: Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy
| Drug: Trametinib |
EXPERIMENTAL: Stage 2 Arm A
| Drug: Naporafenib, Drug: Trametinib |
ACTIVE_COMPARATOR: Stage 2 Arm B - Physician's Choice
| Drug: Dacarbazine, Drug: Temozolomide, Drug: Trametinib |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 6 months from time of first dose |
| Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1 | Assessed up to 6 months from time of first dose |
| Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
| Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Time to achieve maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
| Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Area under the plasma concentration-time curve | Study Day 1 up to Day 29 |
| 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) | * Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1 * Survival status | Assessed up to 24 months from time of first dose |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 24 months from time of first dose |
| Duration of Response (DOR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
| Time to Response (TTR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
| Disease Control Rate (DCR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
| Overall Response Rate (ORR) | Based on the assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose |
| Plasma concentration (Cmax):Stage 1 only | Maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
| Area under the curve (AUC):Stage 1 only | Area under the plasma concentration-time curve | Study Day 1 up to Day 29 |
| Quality of Life: To assess disease and treatment-related QOL in patients with NRASm melanoma. | Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire \[QLQ\]-C30 subscales and PRO CTCAE® symptom items specific to the potential cutaneous toxicities. | Assessed up to 24 months from time of first dose |
References
Clinical Trials Gov: A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)Other trials to consider
Loading suggested trials...
