$0.00
Shopping Cart
Facebook-f Instagram
DONATE
Donate

Clinical Trial Record

Return to Clinical Trials

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations

2023-08-17

2025-07

2025-11

86

Study Overview

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations

To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors * To evaluate the safety and tolerability of naporafenib administered with trametinib in patients with RAS Q61X solid tumors * To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when administered to patients with RAS Q61X solid tumors

SEACRAFT-1 is an open-label study to assess the safety and efficacy of naporafenib administered with trametinib in previously treated patients with locally advanced unresectable or metastatic RAS Q61X solid tumor malignancies. The study will enroll a total of approximately 100 adult patients; a sub-study will enroll approximately 15 adolescent patients ≥12 and <18 years for a total sample size of approximately 115. Patients with a locally advanced unresectable or metastatic solid tumor malignancy that is not responsive to standard therapies or for which there is no standard therapy are eligible. Patients with primary central nervous system (CNS) tumors are not eligible. Documentation of a RAS Q61X mutation in tumor tissue prior to the first dose of study treatment is required.

  • Advanced or Metastatic Solid Tumors
  • DRUG: Naporafenib
  • DRUG: Trametinib
  • ERAS-254-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2023-05-30  

N/A  

2025-05-21  

2023-06-07  

N/A  

2025-05-22  

2023-06-18  

N/A  

2025-05  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Naporafenib + Trametinib

Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)

DRUG: Naporafenib

  • Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor

DRUG: Trametinib

  • Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Primary Outcome MeasuresMeasure DescriptionTime Frame
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumorsBased on assessment of Objective response rate (ORR) per RECIST version 1.1Assessed up to 24 months from time of first dose
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Adverse EventsIncidence and severity of treatment-emergent AEs and serious AEsAssessed up to 24 months from time of first dose
Duration of Response (DOR)Based on assessment of radiographic imaging per RECIST version 1.1Assessed up to 24 months from time of first dose
Time to Response (TTR)Based on assessment of radiographic imaging per RECIST version 1.1Assessed up to 24 months from time of first dose
Progression Free Survival (PFS)Based on assessment of radiographic imaging per RECIST version 1.1Assessed up to 24 months from time of first dose
Disease Control Rate (DCR)Based on assessment of radiographic imaging per RECIST version 1.1Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)Maximum plasma concentration of ERAS-254 and trametinibStudy Day 1 up to Day 29
Time to achieve Cmax (Tmax)Time to achieve maximum plasma concentration of ERAS-254 and trametinibStudy Day 1 up to Day 29
Area under the curve (AUC)Area under the plasma concentration-time curveStudy Day 1 up to Day 29
Overall survivalSurvival StatusAssessed up to 24 months from time of first dose

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
12 Years

Accepts Healthy Volunteers:

    Key Inclusion Criteria:
    1. Willing and able to provide written informed consent 2. Age ≥ 12 years 3. A locally advanced or metastatic tumor who has progressed on or for which no standard therapy exists. Patients who are intolerant to standard therapy or who are not a candidate for standard therapy (in the opinion of the Investigator) or who decline standard therapy are also eligible. 4. Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of study treatment 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. ECOG performance status 0, 1 or 2 7. Presence of at least 1 measurable lesion according to RECIST v1.1 8. Able to swallow oral medication.
    Exclusion Criteria:
    1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor 2. Impairment of GI function or gastrointestinal (GI) disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) 3. 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) 4. Corrected QT interval using Fridericia's formula (QTcF) at Screening >450 ms based on triplicate average NOTE: criterion does not apply to patients with a right or left bundle branch block 5. LVEF <50% 6. All primary CNS tumors 7. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible. 8. Patients receiving treatment with medications that are known to be strong inhibitors and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A with a narrow therapeutic index and sensitive substrates of CYP3A; 9. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

    • STUDY_DIRECTOR: Joyce Antal, MS, Clinical Development

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    No publications available

    NPCF Pop up

    Make-A-Will Month

    Snag 6508be92
    Learn More
    Donate Now Online
    Other Ways to Donate