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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06346067




Registration number
NCT06346067
Ethics application status
Date submitted
17/03/2024
Date registered
3/04/2024
Date last updated
4/11/2024

Titles & IDs
Public title
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
Scientific title
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]
Secondary ID [1] 0 0
ERAS-254-02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic NRAS-mutant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Naporafenib
Treatment: Drugs - Dacarbazine
Treatment: Drugs - Temozolomide
Treatment: Drugs - Trametinib

Experimental: Stage 1 Dose selection Lead-in Arm 1 - Naporafenib + Trametinib Naporafenib (ERAS-254) 100 mg administered orally twice daily (BID) Trametinib 1 mg once daily (QD)

Experimental: Stage 1 Dose selection Lead-in Arm 2 - Naporafenib + Trametinib Naporafenib (ERAS-254) 400 mg administered orally twice daily (BID) Trametinib 0.5 mg once daily (QD)

Active comparator: Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy - Trametinib 2 mg once daily (QD)

Experimental: Stage 2 Arm A - Naporafenib + Trametinib Naporafenib (ERAS-254) BID oral administration with Trametinib QD at the dose selected in Stage 1

Active comparator: Stage 2 Arm B - 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 PO QD


Treatment: Drugs: Naporafenib
Naporafenib (ERAS-254) is an experimental Pan-Raf inhibitor

Treatment: Drugs: Dacarbazine
Dacarbazine IV - Day 1

Treatment: Drugs: Temozolomide
Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle

Treatment: Drugs: Trametinib
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Timepoint [1] 0 0
Assessed up to 6 months from time of first dose
Primary outcome [2] 0 0
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Timepoint [2] 0 0
Assessed up to 6 months from time of first dose
Primary outcome [3] 0 0
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Timepoint [3] 0 0
Study Day 1 up to Day 29
Primary outcome [4] 0 0
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Timepoint [4] 0 0
Study Day 1 up to Day 29
Primary outcome [5] 0 0
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Timepoint [5] 0 0
Study Day 1 up to Day 29
Primary outcome [6] 0 0
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)
Timepoint [6] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [1] 0 0
Adverse Events
Timepoint [1] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Assessed up to 24 months from time of first dose]
Secondary outcome [3] 0 0
Time to Response (TTR)
Timepoint [3] 0 0
Assessed up to 24 months from time of first dose]
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Assessed up to 24 months from time of first dose]
Secondary outcome [5] 0 0
Overall Response Rate (ORR)
Timepoint [5] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [6] 0 0
Plasma concentration (Cmax):Stage 1 only
Timepoint [6] 0 0
Study Day 1 up to Day 29
Secondary outcome [7] 0 0
Area under the curve (AUC):Stage 1 only
Timepoint [7] 0 0
Study Day 1 up to Day 29
Secondary outcome [8] 0 0
Quality of Life: To assess disease and treatment-related QOL in patients with NRASm melanoma.
Timepoint [8] 0 0
Assessed up to 24 months from time of first dose

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
470
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Tasman Health Care - Southport
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Czechia
State/province [13] 0 0
Nový Hradec Králové
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague
Country [15] 0 0
France
State/province [15] 0 0
Le Mans
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Netherlands
State/province [17] 0 0
Nijmegen
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Erasca, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/study/NCT06346067
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joyce Antal
Address 0 0
Clinical Development
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Erasca Clinical Team
Address 0 0
Country 0 0
Phone 0 0
1-858-465-6511
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06346067