Advanced or Metastatic Solid TumorsPhase 1SEACRAFT-1NCT05907304
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations
A Phase 1 study testing Naporafenib and Trametinib in people with Advanced or Metastatic Solid Tumors, run by Erasca, Inc. at 29 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 to 99 years
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- Naporafenib and Trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 29 sitesin 5 countries
- Study dates
- 17 Aug 2023to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent
- Age ≥ 12 years
- 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.
- 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.
- 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.
- ECOG performance status 0, 1 or 2
- Presence of at least 1 measurable lesion according to RECIST v1.1
- Able to swallow oral medication.
Who cannot join
- Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
- 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)
- 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)
- 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
- LVEF <50%
- All primary CNS tumors
Show all 9Show fewer
- Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
- 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;
- Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
United States14 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Henry Ford Health System
Detroit, Michigan, 48202
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
NEXT Virginia
Fairfax, Virginia, 22031
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Comprehensive Cancer Center of Nevada (CCCN)
Las Vegas, Nevada, 89169
University of Wisconsin
Madison, Wisconsin, 53792
SCRI Oncology Partners (formerly Tennessee Oncology)
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06510
Oregon Health & Science University
Portland, Oregon, 97239
University of California, San Francisco
San Francisco, California, 94143
Florida Cancer Specialists - Sarasota
Sarasota, Florida, 34232
Washington University School of Medicine
St Louis, Missouri, 63110
Florida Cancer Specialists - St. Petersburg
St. Petersburg, Florida, 33705
South Korea6 sites
Inje University Haeundae Paik Hospital
Busan, Busan Gwang'yeogsi, 48108
National Cancer Center
Goyang-si
Seoul National University Hospital Bundang
Gyeonggi-do
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351
Seoul National University Hospital
Seoul
The Catholic University Hospital
Seoul
Canada4 sites
Cross Cancer Institute- Alberta Health Services (AHS)
Edmonton, Alberta, T6G 1Z2
London Regional Cancer Center
London, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 4E6
Australia3 sites
Macquarie University
Macquarie Park, New South Wales
St. Vincent's Hospital
Melbourne, Victoria
Linear Clinical Research, LTD
Perth
United Kingdom2 sites
Sarah Cannon Research Institute - HCA Healthcare
City of London, London, W1G 6AD
Beatson West of Scotland Cancer Center
Glasgow
About this study
Official title: 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
Read the 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.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- Naporafenib, Trametinib
- Keywords
- Melanoma, Non-small cell lung cancer, Thyroid cancer, Colorectal Cancer (cohort full), Pancreatic Cancer, Other solid tumors harboring a RAS Q61X mutation
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms, Colorectal Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaporafenibDrug
Also called LXH254, ERAS-254
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor
TrametinibDrug
Also called Mekinist
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
| Study group | Role | What they receive |
|---|---|---|
| Naporafenib + Trametinib | Experimental | Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD) Receives: Drug: Naporafenib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
Based on assessment of Objective response rate (ORR) per RECIST version 1.1
Measured: Assessed up to 24 months from time of first dose
Secondary outcomes (9)
Adverse Events
Incidence and severity of treatment-emergent AEs and serious AEs
Measured: 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
Measured: 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
Measured: Assessed up to 24 months from time of first dose
Progression Free Survival (PFS)
Based on assessment of radiographic imaging per RECIST version 1.1
Measured: 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
Measured: Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)
Maximum plasma concentration of ERAS-254 and trametinib
Measured: Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)
Time to achieve maximum plasma concentration of ERAS-254 and trametinib
Measured: Study Day 1 up to Day 29
Area under the curve (AUC)
Area under the plasma concentration-time curve
Measured: Study Day 1 up to Day 29
Overall survival
Survival Status
Measured: Assessed up to 24 months from time of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start17 Aug 2023
- Primary completion1 Jul 2025
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasca, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joyce Antal, MS, Study director, Clinical Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05907304
- Sponsor's protocol ID
- ERAS-254-01
- Acronym
- SEACRAFT-1
- Status last verified
- Feb 2026
- First submitted
- 30 May 2023
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05907304
- Acronym / sponsor ID
- SEACRAFT-1 / ERAS-254-01
- Conditions
- Advanced or Metastatic Solid Tumors
- Keywords
- Melanoma, Non-small cell lung cancer, Thyroid cancer, Colorectal Cancer (cohort full), Pancreatic Cancer, Other solid tumors harboring a RAS Q61X mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Erasca, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Aug 2023 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 18 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Naporafenib + Trametinib | Experimental | Drug: Naporafenib, Drug: TrametinibNaporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD) |
Who may qualify
- Ages
- 12 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to provide written informed consent
- Age ≥ 12 years
- 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.
- 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.
- 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.
Key exclusion criteria (9 listed)
- Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
- 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)
- 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)
- 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
- LVEF <50%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaporafenibAlso: LXH254, ERAS-254Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor | Drug | Naporafenib + Trametinib |
| TrametinibAlso: MekinistTrametinib is an FDA approved anticancer medication that targets MEK1 and MEK2. | Drug | Naporafenib + Trametinib |
Primary outcome
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
9 secondary outcomes
Adverse Events
Time frame: 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
Time to Response (TTR)
Time frame: 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
Disease Control Rate (DCR)
Time frame: Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)
Time frame: Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)
Time frame: Study Day 1 up to Day 29
Area under the curve (AUC)
Time frame: Study Day 1 up to Day 29
Overall survival
Time frame: Assessed up to 24 months from time of first dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joyce Antal, MS study director
Clinical Development
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Naporafenib and Trametinib in people with Advanced or Metastatic Solid Tumors, run by Erasca, Inc. at 29 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, South Korea, Canada, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.