A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (SEACRAFT-1)

February 24, 2026 updated by: Erasca, Inc.

An Open-label Study to Assess the Safety and Efficacy of Naporafenib (ERAS-254) Administered With Trametinib in Previously Treated Patients With Locally Advanced Unresectable or Metastatic Solid Tumor Malignancies 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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
86

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
      • Perth, Australia
        • Linear Clinical Research, LTD
    • New South Wales
      • Macquarie Park, New South Wales, Australia
        • Macquarie University
    • Victoria
      • Melbourne, Victoria, Australia
        • St. Vincent's Hospital
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute- Alberta Health Services (AHS)
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency
    • Ontario
      • London, Ontario, Canada
        • London Regional Cancer Center
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
  • South Korea
      • Goyang-si, South Korea
        • National Cancer Center
      • Gyeonggi-do, South Korea
        • Seoul National University Hospital Bundang
      • Seoul, South Korea
        • Seoul National University Hospital
      • Seoul, South Korea
        • The Catholic University Hospital
    • Busan Gwang'yeogsi
      • Busan, Busan Gwang'yeogsi, South Korea, 48108
        • Inje University Haeundae Paik Hospital
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, South Korea, 06351
        • Samsung Medical Center
  • United Kingdom
      • Glasgow, United Kingdom
        • Beatson West of Scotland Cancer Center
    • London
      • City of London, London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute - HCA Healthcare
  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Cancer Center
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists - Sarasota
      • St. Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists - St. Petersburg
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Center of Nevada (CCCN)
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI Oncology Partners (formerly Tennessee Oncology)
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Fairfax, Virginia, United States, 22031
        • NEXT Virginia
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Naporafenib + Trametinib
Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)
Drug: Trametinib
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Other Names:
  • Mekinist
Drug: Naporafenib
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor
Other Names:
  • LXH254
  • ERAS-254

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
Time Frame: Assessed up to 24 months from time of first dose
Based on assessment of Objective response rate (ORR) per RECIST version 1.1
Assessed up to 24 months from time of first dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
Assessed up to 24 months from time of first dose
Duration of Response (DOR)
Time Frame: Assessed up to 24 months from time of first dose
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)
Time Frame: Assessed up to 24 months from time of first dose
Based on assessment of radiographic imaging per RECIST version 1.1
Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)
Time Frame: Study Day 1 up to Day 29
Maximum plasma concentration of ERAS-254 and trametinib
Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)
Time Frame: Study Day 1 up to Day 29
Time to achieve maximum plasma concentration of ERAS-254 and trametinib
Study Day 1 up to Day 29
Area under the curve (AUC)
Time Frame: Study Day 1 up to Day 29
Area under the plasma concentration-time curve
Study Day 1 up to Day 29
Overall survival
Time Frame: Assessed up to 24 months from time of first dose
Survival Status
Assessed up to 24 months from time of first dose
Progression Free Survival (PFS)
Time Frame: Assessed up to 24 months from time of first dose
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)
Time Frame: Assessed up to 24 months from time of first dose
Based on assessment of radiographic imaging per RECIST version 1.1
Assessed up to 24 months from time of first dose

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) for CNS disease in participants
Time Frame: Assessed up to 24 months from time of first dose
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
Assessed up to 24 months from time of first dose
Overall Response Rate (ORR) for CNS disease in participants
Time Frame: Assessed up to 24 months from time of first dose
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
Assessed up to 24 months from time of first dose
Disease Control Rate (DCR) for CNS disease in participants
Time Frame: Assessed up to 24 months from time of first dose
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
Assessed up to 24 months from time of first dose
Pharmacodynamic assessment
Time Frame: Assessed up to 24 months from time of first dose
DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition.
Assessed up to 24 months from time of first dose

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erasca, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Joyce Antal, MS, Clinical Development

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 17, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ERAS-254-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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