Ignite Creation Date:
2025-12-25 @ 1:43 AM
Ignite Modification Date:
2025-12-26 @ 12:00 AM
Study NCT ID:
NCT05375994
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-05-18
First Post:
2022-05-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D009369', 'term': 'Neoplasms'}], 'ancestors': [{'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000718190', 'term': 'adagrasib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 85}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2022-08-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2026-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-13', 'studyFirstSubmitDate': '2022-05-02', 'studyFirstSubmitQcDate': '2022-05-10', 'lastUpdatePostDateStruct': {'date': '2025-05-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-05-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-24', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib', 'timeFrame': 'From start of treatment to confirmation of RP2D; 28 days', 'description': 'Assessment of Dose-limiting toxicities (DLTs)'}, {'measure': 'To determine the efficacy of the optimal regimen identified from Part A', 'timeFrame': 'From start of treatment to confirmation of response; 16 weeks', 'description': 'Confirmed overall response rate per RECIST 1.1'}], 'secondaryOutcomes': [{'measure': 'To characterize the safety and toxicity profile:', 'timeFrame': '24 Months', 'description': '* Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)\n* Severity of Adverse events (AEs) and Serious Adverse Events (SAEs) by toxicity grade assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)\n* Duration of Adverse events (AEs) and Serious Adverse Events (SAEs)\n* Incidence of clinically significant changes in lab parameters\n* Incidence of abnormal vital signs (including systolic and diastolic blood pressure in mmHg)'}, {'measure': 'ECG QT Interval', 'timeFrame': '24 months', 'description': 'Corrected ECG QT interval by Fredericia (QTcF)'}, {'measure': 'Duration of Response (DOR)', 'timeFrame': 'Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months', 'description': 'Time of first response to PD as assessed per RECIST 1.1'}, {'measure': 'Disease Control Rate (DCR)', 'timeFrame': 'Greater than or equal to 8 weeks', 'description': 'CR and PR stable disease as assessed per RECIST 1.1'}, {'measure': 'Progression Free Survival (PFS)', 'timeFrame': '24 months', 'description': 'From the time of first dose of study intervention to PD or death from any cause'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Up to 5 years', 'description': 'From time of first dose of study intervention to death'}, {'measure': 'Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax', 'timeFrame': '10 weeks', 'description': 'time of Maximum concentration (Tmax)'}, {'measure': 'Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC', 'timeFrame': '10 weeks', 'description': 'Area under plasma Concentration (AUC) 0 to t'}, {'measure': 'Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life', 'timeFrame': '10 weeks', 'description': 'concentration Half-life (T1/2)'}, {'measure': 'Clinical Benefit Rate', 'timeFrame': '≥ 6 months', 'description': 'defined as Complete Response+Partial Response +Stable Disease'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['NSCLC', 'KRAS G12C', 'Non Small Cell Lung Cancer', 'Metastatic Cancer', 'Adagrasib', 'Avutometinib (VS-6766)'], 'conditions': ['Non Small Cell Lung Cancer', 'KRAS Activating Mutation', 'Advanced Cancer', 'Metastatic Cancer', 'Malignant Neoplasm of Lung', 'Malignant Neoplastic Disease']}, 'descriptionModule': {'briefSummary': 'This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.', 'detailedDescription': 'This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female subjects ≥ 18 years of age\n* Histologic or cytologic evidence of NSCLC\n* Known KRAS G12C mutation\n* The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression\n* Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 prior regimens, for Stage 3B-C or 4 NSCLC\n* Measurable disease according to RECIST 1.1\n* An Eastern Cooperative Group (ECOG) performance status ≤ 1\n* Adequate organ function\n* Adequate recovery from toxicities related to prior treatments\n* Agreement to use highly effective method of contraceptive\n\nExclusion Criteria:\n\n* Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation \\> 30Gy)\n* History of prior malignancy, with the exception of curatively treated malignancies\n* Major surgery within 4 weeks (excluding placement of vascular access)\n* Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy\n* Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy\n* Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy\n* Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy\n* Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active\n* Active skin disorder that has required systemic therapy within the past 1 year\n* History of rhabdomyolysis or interstitial lung disease\n* Concurrent ocular disorders\n* Concurrent heart disease or severe obstructive pulmonary disease\n* Subjects with the inability to swallow oral medications'}, 'identificationModule': {'nctId': 'NCT05375994', 'acronym': 'RAMP204', 'briefTitle': 'Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Verastem, Inc.'}, 'officialTitle': 'A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)', 'orgStudyIdInfo': {'id': 'VS-6766-204'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'avutometinib(VS-6766)+adagrasib', 'description': 'To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients', 'interventionNames': ['Drug: avutometinib (VS-6766) and adagrasib']}, {'type': 'EXPERIMENTAL', 'label': 'avutometinib (VS-6766)+adagrasib RP2D', 'description': 'To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients', 'interventionNames': ['Drug: avutometinib (VS-6766) and adagrasib']}], 'interventions': [{'name': 'avutometinib (VS-6766) and adagrasib', 'type': 'DRUG', 'otherNames': ['KRAS G12C Inhibitor, adagrasib, KRAZATI®'], 'description': 'The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion', 'armGroupLabels': ['avutometinib (VS-6766)+adagrasib RP2D', 'avutometinib(VS-6766)+adagrasib']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94158', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'UCSF Thoracic Oncology', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Hospital Anschutz Cancer Pavllion', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '32224', 'city': 'Jacksonville', 'state': 'Florida', 'country': 'United States', 'facility': 'Mayo Clinic Cancer Center', 'geoPoint': {'lat': 30.33218, 'lon': -81.65565}}, {'zip': '55905', 'city': 'Rochester', 'state': 'Minnesota', 'country': 'United States', 'facility': 'Mayo Clinic Cancer Center', 'geoPoint': {'lat': 44.02163, 'lon': -92.4699}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '275514', 'city': 'Chapel Hill', 'state': 'North Carolina', 'country': 'United States', 'facility': 'University of North Carolina at Chapel Hill', 'geoPoint': {'lat': 35.9132, 'lon': -79.05584}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'Virginia Cancer Specialists, NEXT Oncology', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}, {'zip': '53226', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'Medical College Wisconsin', 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}], 'overallOfficials': [{'name': 'MD Verastem', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Verastem, Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Verastem, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Mirati Therapeutics Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}