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

Get Involved

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

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	12 Years - 99 Years
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05907304
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Erasca, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Joyce Antal, MS
Principal Investigator Affiliation	Clinical Development
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Active, not recruiting
Countries	Australia, Canada, South Korea, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Advanced or Metastatic Solid Tumors

Additional Details

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.

Arms & Interventions

Arms

Experimental: Naporafenib + Trametinib

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

Interventions

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of California, San Francisco, San Francisco 5391959, California 5332921

Status

Address

University of California, San Francisco

San Francisco 5391959, California 5332921, 94143

Yale Cancer Center, New Haven 4839366, Connecticut 4831725

Status

Address

Yale Cancer Center

New Haven 4839366, Connecticut 4831725, 06510

Florida Cancer Specialists - Sarasota, Sarasota 4172131, Florida 4155751

Status

Address

Florida Cancer Specialists - Sarasota

Sarasota 4172131, Florida 4155751, 34232

St. Petersburg 4171563, Florida 4155751

Status

Address

Florida Cancer Specialists - St. Petersburg

St. Petersburg 4171563, Florida 4155751, 33705

Emory University School of Medicine, Atlanta 4180439, Georgia 4197000

Status

Address

Emory University School of Medicine

Atlanta 4180439, Georgia 4197000, 30322

Henry Ford Health System, Detroit 4990729, Michigan 5001836

Status

Address

Henry Ford Health System

Detroit 4990729, Michigan 5001836, 48202

Washington University School of Medicine, St Louis 4407066, Missouri 4398678

Status

Address

Washington University School of Medicine

St Louis 4407066, Missouri 4398678, 63110

Las Vegas 5506956, Nevada 5509151

Status

Address

Comprehensive Cancer Center of Nevada (CCCN)

Las Vegas 5506956, Nevada 5509151, 89169

Oregon Health & Science University, Portland 5746545, Oregon 5744337

Status

Address

Oregon Health & Science University

Portland 5746545, Oregon 5744337, 97239

Nashville 4644585, Tennessee 4662168

Status

Address

SCRI Oncology Partners (formerly Tennessee Oncology)

Nashville 4644585, Tennessee 4662168, 37203

Houston 4699066, Texas 4736286

Status

Address

The University of Texas MD Anderson Cancer Center

Houston 4699066, Texas 4736286, 77030

Inova Schar Cancer Institute, Fairfax 4758023, Virginia 6254928

Status

Address

Inova Schar Cancer Institute

Fairfax 4758023, Virginia 6254928, 22031

NEXT Virginia, Fairfax 4758023, Virginia 6254928

Status

Address

NEXT Virginia

Fairfax 4758023, Virginia 6254928, 22031

University of Wisconsin, Madison 5261457, Wisconsin 5279468

Status

Address

University of Wisconsin

Madison 5261457, Wisconsin 5279468, 53792

International Sites

Macquarie University, Macquarie Park 8347858, New South Wales 2155400, Australia

Status

Address

Macquarie University

Macquarie Park 8347858, New South Wales 2155400,

St. Vincent's Hospital, Melbourne 2158177, Victoria 2145234, Australia

Status

Address

St. Vincent's Hospital

Melbourne 2158177, Victoria 2145234,

Linear Clinical Research, LTD, Perth 2063523, Australia

Status

Address

Linear Clinical Research, LTD

Perth 2063523, ,

Edmonton 5946768, Alberta 5883102, Canada

Status

Address

Cross Cancer Institute- Alberta Health Services (AHS)

Edmonton 5946768, Alberta 5883102, T6G 1Z2

British Columbia Cancer Agency, Vancouver 6173331, British Columbia 5909050, Canada

Status

Address

British Columbia Cancer Agency

Vancouver 6173331, British Columbia 5909050, V5Z 4E6

London Regional Cancer Center, London 6058560, Ontario 6093943, Canada

Status

Address

London Regional Cancer Center

London 6058560, Ontario 6093943,

Princess Margaret Cancer Centre, Toronto 6167865, Ontario 6093943, Canada

Status

Address

Princess Margaret Cancer Centre

Toronto 6167865, Ontario 6093943, M5G 2M9

Inje University Haeundae Paik Hospital, Busan 1838524, Busan Gwang'yeogsi, South Korea

Status

Address

Inje University Haeundae Paik Hospital

Busan 1838524, Busan Gwang'yeogsi, 48108

Samsung Medical Center, Seoul 1835848, Seoul Teugbyeolsi, South Korea

Status

Address

Samsung Medical Center

Seoul 1835848, Seoul Teugbyeolsi, 06351

National Cancer Center, Goyang-si 1842485, South Korea

Status

Address

National Cancer Center

Goyang-si 1842485, ,

Gyeonggi-do 6363696, South Korea

Status

Address

Seoul National University Hospital Bundang

Gyeonggi-do 6363696, ,

Seoul National University Hospital, Seoul 1835848, South Korea

Status

Address

Seoul National University Hospital

Seoul 1835848, ,

The Catholic University Hospital, Seoul 1835848, South Korea

Status

Address

The Catholic University Hospital

Seoul 1835848, ,

City of London 2643741, London, United Kingdom

Status

Address

Sarah Cannon Research Institute - HCA Healthcare

City of London 2643741, London, W1G 6AD

Beatson West of Scotland Cancer Center, Glasgow 2648579, United Kingdom

Status

Address

Beatson West of Scotland Cancer Center

Glasgow 2648579, ,

Clinical Trial Finder