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

NCT ID: NCT05907304

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-17
• Study Completion Date: 2025-11-30

Brief 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 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.

Conditions

Advanced or Metastatic Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Naporafenib + Trametinib

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

Group Type: EXPERIMENTAL

Naporafenib

Intervention Type: DRUG

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

Trametinib

Intervention Type: DRUG

Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.

Interventions

Naporafenib

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

Intervention Type: DRUG

Trametinib

Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.

Intervention Type: DRUG

Other Intervention Names

LXH254; ERAS-254; Mekinist

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasca, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joyce Antal, MS

Role: STUDY_DIRECTOR

Clinical Development

Locations

University of California, San Francisco

San Francisco, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Florida Cancer Specialists - Sarasota

Sarasota, Florida, United States

Florida Cancer Specialists - St. Petersburg

St. Petersburg, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Henry Ford Health System

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Comprehensive Cancer Center of Nevada (CCCN)

Las Vegas, Nevada, United States

Oregon Health & Science University

Portland, Oregon, United States

SCRI Oncology Partners (formerly Tennessee Oncology)

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Inova Schar Cancer Institute

Fairfax, Virginia, United States

NEXT Virginia

Fairfax, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

Macquarie University

Macquarie Park, New South Wales, Australia

St. Vincent's Hospital

Melbourne, Victoria, Australia

Linear Clinical Research, LTD

Perth, , Australia

Cross Cancer Institute- Alberta Health Services (AHS)

Edmonton, Alberta, Canada

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

London Regional Cancer Center

London, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Inje University Haeundae Paik Hospital

Busan, Busan Gwang'yeogsi, South Korea

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

National Cancer Center

Goyang-si, , South Korea

Seoul National University Hospital Bundang

Gyeonggi-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

The Catholic University Hospital

Seoul, , South Korea

Sarah Cannon Research Institute - HCA Healthcare

City of London, London, United Kingdom

Beatson West of Scotland Cancer Center

Glasgow, , United Kingdom

Countries

United States; Australia; Canada; South Korea; United Kingdom

Other Identifiers

ERAS-254-01

Identifier Type: -

Identifier Source: org_study_id