Ignite Creation Date:
2025-12-24 @ 7:51 PM
Ignite Modification Date:
2025-12-27 @ 1:12 PM
Study NCT ID:
NCT05907304
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-05-22
First Post:
2023-05-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}, {'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}, {'id': 'D013964', 'term': 'Thyroid Neoplasms'}, {'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D010190', 'term': 'Pancreatic Neoplasms'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D013959', 'term': 'Thyroid Diseases'}, {'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}, {'id': 'D010182', 'term': 'Pancreatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000723373', 'term': 'naporafenib'}, {'id': 'C560077', 'term': 'trametinib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 86}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2023-08-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2025-11', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-21', 'studyFirstSubmitDate': '2023-05-30', 'studyFirstSubmitQcDate': '2023-06-07', 'lastUpdatePostDateStruct': {'date': '2025-05-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-06-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Duration of Response (DOR) for CNS disease in participants', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)'}, {'measure': 'Overall Response Rate (ORR) for CNS disease in participants', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)'}, {'measure': 'Disease Control Rate (DCR) for CNS disease in participants', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)'}, {'measure': 'Pharmacodynamic assessment', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition.'}], 'primaryOutcomes': [{'measure': 'To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on assessment of Objective response rate (ORR) per RECIST version 1.1'}], 'secondaryOutcomes': [{'measure': 'Adverse Events', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Incidence and severity of treatment-emergent AEs and serious AEs'}, {'measure': 'Duration of Response (DOR)', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on assessment of radiographic imaging per RECIST version 1.1'}, {'measure': 'Time to Response (TTR)', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on assessment of radiographic imaging per RECIST version 1.1'}, {'measure': 'Progression Free Survival (PFS)', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on assessment of radiographic imaging per RECIST version 1.1'}, {'measure': 'Disease Control Rate (DCR)', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Based on assessment of radiographic imaging per RECIST version 1.1'}, {'measure': 'Plasma concentration (Cmax)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Maximum plasma concentration of ERAS-254 and trametinib'}, {'measure': 'Time to achieve Cmax (Tmax)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Time to achieve maximum plasma concentration of ERAS-254 and trametinib'}, {'measure': 'Area under the curve (AUC)', 'timeFrame': 'Study Day 1 up to Day 29', 'description': 'Area under the plasma concentration-time curve'}, {'measure': 'Overall survival', 'timeFrame': 'Assessed up to 24 months from time of first dose', 'description': 'Survival Status'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Melanoma', 'Non-small cell lung cancer', 'Thyroid cancer', 'Colorectal Cancer (cohort full)', 'Pancreatic Cancer', 'Other solid tumors harboring a RAS Q61X mutation'], 'conditions': ['Advanced or Metastatic Solid Tumors']}, 'descriptionModule': {'briefSummary': 'To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors\n\n* To evaluate the safety and tolerability of naporafenib administered with trametinib in patients with RAS Q61X solid tumors\n* To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when administered to patients with RAS Q61X solid tumors', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Key Inclusion Criteria:\n\n1. Willing and able to provide written informed consent\n2. Age ≥ 12 years\n3. 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.\n4. 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.\n5. 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.\n6. ECOG performance status 0, 1 or 2\n7. Presence of at least 1 measurable lesion according to RECIST v1.1\n8. Able to swallow oral medication.\n\nExclusion Criteria:\n\n1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor\n2. 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)\n3. 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)\n4. 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\n5. LVEF \\<50%\n6. All primary CNS tumors\n7. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.\n8. 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;\n9. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial"}, 'identificationModule': {'nctId': 'NCT05907304', 'acronym': 'SEACRAFT-1', 'briefTitle': 'A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations', 'organization': {'class': 'INDUSTRY', 'fullName': 'Erasca, Inc.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'ERAS-254-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Naporafenib + Trametinib', 'description': 'Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)', 'interventionNames': ['Drug: Naporafenib', 'Drug: Trametinib']}], 'interventions': [{'name': 'Naporafenib', 'type': 'DRUG', 'otherNames': ['LXH254', 'ERAS-254'], 'description': 'Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor', 'armGroupLabels': ['Naporafenib + Trametinib']}, {'name': 'Trametinib', 'type': 'DRUG', 'otherNames': ['Mekinist'], 'description': 'Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.', 'armGroupLabels': ['Naporafenib + Trametinib']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '06510', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Yale Cancer Center', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '34232', 'city': 'Sarasota', 'state': 'Florida', 'country': 'United States', 'facility': 'Florida Cancer Specialists - Sarasota', 'geoPoint': {'lat': 27.33643, 'lon': -82.53065}}, {'zip': '33705', 'city': 'St. Petersburg', 'state': 'Florida', 'country': 'United States', 'facility': 'Florida Cancer Specialists - St. Petersburg', 'geoPoint': {'lat': 27.77086, 'lon': -82.67927}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University School of Medicine', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '48202', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Henry Ford Health System', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '89169', 'city': 'Las Vegas', 'state': 'Nevada', 'country': 'United States', 'facility': 'Comprehensive Cancer Center of Nevada (CCCN)', 'geoPoint': {'lat': 36.17497, 'lon': -115.13722}}, {'zip': '97239', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health & Science University', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '37203', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'SCRI Oncology Partners (formerly Tennessee Oncology)', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'Inova Schar Cancer Institute', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'NEXT Virginia', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}, {'zip': '53792', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}, {'city': 'Macquarie Park', 'state': 'New South Wales', 'country': 'Australia', 'facility': 'Macquarie University', 'geoPoint': {'lat': -33.78105, 'lon': 151.12757}}, {'city': 'Melbourne', 'state': 'Victoria', 'country': 'Australia', 'facility': "St. Vincent's Hospital", 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'city': 'Perth', 'country': 'Australia', 'facility': 'Linear Clinical Research, LTD', 'geoPoint': {'lat': -31.95224, 'lon': 115.8614}}, {'zip': 'T6G 1Z2', 'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': 'Cross Cancer Institute- Alberta Health Services (AHS)', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'zip': 'V5Z 4E6', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': 'British Columbia Cancer Agency', 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': 'London Regional Cancer Center', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Princess Margaret Cancer Centre', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '48108', 'city': 'Busan', 'state': "Busan Gwang'yeogsi", 'country': 'South Korea', 'facility': 'Inje University Haeundae Paik Hospital', 'geoPoint': {'lat': 35.10168, 'lon': 129.03004}}, {'zip': '06351', 'city': 'Seoul', 'state': 'Seoul Teugbyeolsi', 'country': 'South Korea', 'facility': 'Samsung Medical Center', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Goyang-si', 'country': 'South Korea', 'facility': 'National Cancer Center', 'geoPoint': {'lat': 37.65639, 'lon': 126.835}}, {'city': 'Gyeonggi-do', 'country': 'South Korea', 'facility': 'Seoul National University Hospital Bundang', 'geoPoint': {'lat': 37.58944, 'lon': 126.76917}}, {'city': 'Seoul', 'country': 'South Korea', 'facility': 'Seoul National University Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Seoul', 'country': 'South Korea', 'facility': 'The Catholic University Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'zip': 'W1G 6AD', 'city': 'City of London', 'state': 'London', 'country': 'United Kingdom', 'facility': 'Sarah Cannon Research Institute - HCA Healthcare', 'geoPoint': {'lat': 51.51279, 'lon': -0.09184}}, {'city': 'Glasgow', 'country': 'United Kingdom', 'facility': 'Beatson West of Scotland Cancer Center', 'geoPoint': {'lat': 55.86515, 'lon': -4.25763}}], 'overallOfficials': [{'name': 'Joyce Antal, MS', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Clinical Development'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Erasca, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}