[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT04092673":3,"trial-entities:NCT04092673":334,"trial-summary:NCT04092673":342},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":21,"primary_purpose":22,"phases":23,"enrollment_info":26,"interventions":29,"primary_outcomes":72,"secondary_outcomes":106,"sex":141,"minimum_age":142,"maximum_age":15,"healthy_volunteers":143,"eligibility_criteria":144,"std_ages":148,"locations":151,"central_contacts":322,"overall_officials":327,"references":332,"see_also_links":333},"NCT04092673","eFT226-0002","Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies","A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies","UNKNOWN","2025-03-31","2024-05","2024-05-21","2019-10-25","Effector Therapeutics","INDUSTRY",null,"This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor malignancies.","Part 1 (Dose Escalation): Completed; Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) identified\n\nPart 1a (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy.\n\nPart 1b (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy.\n\nPart 2 (Expansion Cohort) provides defined expansion cohorts to further explore the safety, pharmacology, and clinical activity of eFT226 monotherapy and in various combinations in subjects with previously treated advanced solid tumor malignancies.",[19],"Solid Tumor, Adult",[],"INTERVENTIONAL","TREATMENT",[24,25],"PHASE1","PHASE2",{"count":27,"type":28},30,"ESTIMATED",[30,41,48,59,65],{"type":31,"name":32,"description":33,"armGroupLabels":34,"otherNames":39},"DRUG","eFT226","eFT226 is a novel small-molecule, investigational drug being developed by eFFECTOR Therapeutics as an anticancer therapy. eFT226 is a potent and selective inhibitor of eIF4A1-mediated translation and selectively regulates the translation of a subset of mRNAs based on sequence specific recognition motifs in their 5'-UTR. eIF4A1 inhibition by eFT226 downregulates expression of receptor tyrosine kinases and KRAS, leading to decreased signaling through the PI3K\u002FAKT and MAPK pathways. Preclinical efficacy testing of eFT226 demonstrates activity across models of solid tumor cancers with amplifications in HER2, FGFR1\u002F2 and mutations in KRAS (including breast, NSCLC and CRC).",[35,36,37,38],"Part 1: Sequential escalation (Completed)","Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)","Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)","Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)",[40],"Selective translation inhibitor",{"type":31,"name":42,"description":43,"armGroupLabels":44,"otherNames":46},"Sotorasib","Recommended dosage: 960 mg orally once daily",[45],"Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)",[47],"Lumarkus",{"type":31,"name":49,"description":50,"armGroupLabels":51,"otherNames":57},"Fulvestrant","500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter",[52,53,54,55,56],"Part 1a: Dose Escalation, Combination, Breast","Part 1b Dose Escalation, Combination, Breast","Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1","Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)","Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)",[58],"Faslodex",{"type":31,"name":60,"description":61,"armGroupLabels":62,"otherNames":63},"Abemaciclib","Dose in combination with fulvestrant: 150 mg twice daily",[56],[64],"Verzenia",{"type":31,"name":66,"description":67,"armGroupLabels":68,"otherNames":70},"Trastuzumab","600 mg every 3 weeks",[69],"Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)",[71],"Herceptin",[73,77,80,83,85,88,91,94,97,100,103],{"measure":74,"description":75,"timeFrame":76},"Parts 1a and 1b: MTD","determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design","Through study completion, approximately 12 months",{"measure":78,"description":79,"timeFrame":76},"Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs","according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)",{"measure":81,"description":82,"timeFrame":76},"Parts 1a and 1b: RP2D","determined by Incidence and type of DLTs",{"measure":81,"description":84,"timeFrame":76},"determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE",{"measure":86,"description":87,"timeFrame":76},"Part 2: Objective Response Rate- Efficacy","defined as confirmed Complete Response (CR) or Partial Response (PR)",{"measure":89,"description":90,"timeFrame":76},"Part 2: (Combination Cohorts) Determine MTD","determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design",{"measure":92,"description":93,"timeFrame":76},"Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs","via adverse event monitoring",{"measure":95,"description":96,"timeFrame":76},"Part 2: (Combination Cohorts) Determine RP2D","determined by incidence and type of DLTs, and incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)",{"measure":98,"description":99,"timeFrame":76},"Part 2: Percent change in tumor dimensions of target lesions- Efficacy","calculated by the percentage change from baseline in the sum of the LD of target lesions",{"measure":101,"description":102,"timeFrame":76},"Part 2: Time to Response (TTR)- Efficacy","defined as the interval from the start of study therapy to the first documentation of an objective response",{"measure":104,"description":105,"timeFrame":76},"Part 2: Duration of Response (DOR)- Efficacy","defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause",[107,110,112,114,116,119,121,123,126,128,130,132,134,136,139],{"measure":108,"description":109,"timeFrame":76},"Parts 1a and 1b: Objective response","determined by confirmed CR or PR",{"measure":111,"description":99,"timeFrame":76},"Parts 1a and 1b: Percent change in tumor dimensions of target lesions",{"measure":113,"description":102,"timeFrame":76},"Parts 1a and 1b: TTR",{"measure":115,"description":105,"timeFrame":76},"Parts 1a and 1b: DOR",{"measure":117,"description":118,"timeFrame":76},"Parts 1a and 1b: PFS","defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause",{"measure":120,"description":93,"timeFrame":76},"Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters",{"measure":122,"description":118,"timeFrame":76},"Part 2: Progression Free Survival",{"measure":124,"description":125,"timeFrame":76},"Evaluate plasma Pharmacokinetic (PK) parameters of eFT226","including area under the plasma concentration-time curve",{"measure":124,"description":127,"timeFrame":76},"including maximum concentration",{"measure":124,"description":129,"timeFrame":76},"including terminal phase rate constant",{"measure":124,"description":131,"timeFrame":76},"including estimated steady-state volume of distribution \\[Vss\\]",{"measure":124,"description":133,"timeFrame":76},"including half-life (t½)",{"measure":124,"description":135,"timeFrame":76},"including total body clearance",{"measure":137,"description":138,"timeFrame":76},"Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution","including terminal state volume of distribution",{"measure":140,"description":129,"timeFrame":76},"Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant","ALL","18 Years",false,{"inclusion":145,"exclusion":146,"raw_text":147},[],[],"Key Criteria:\n\nParts 1a and 1b (Dose Escalation + Fulvestrant):\n\n* Patient has histological or cytological confirmation of breast cancer.\n* Patient has metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit.\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Maximum of five prior lines of therapy for advanced\u002Fmetastatic disease.\n  * Recurrence or progression on at least one line of endocrine therapy in the advanced\u002Fmetastatic disease setting.\n  * Prior treatment has included a CDK4\u002F6 inhibitor.\n* Tumor is ER+ (defined as ER IHC staining \\> 0%).\n\nCohort EMNK:\n\n* Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1\u002FL1 agent, if appropriate.\n* Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are excluded.\n\nCohort EMBF:\n\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Maximum of five prior lines of therapy for advanced\u002Fmetastatic disease.\n  * Recurrence or progression on at least one line of endocrine therapy in the advanced\u002Fmetastatic disease setting, which may include combination therapy (eg, with a CDK4\u002F6 inhibitor).\n* Tumor is ER+ (defined as ER IHC staining \\> 0%) and has FGFR amplification.\n\nCohort EMBH:\n\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4\u002F6 inhibitors is permitted.\n* Tumor is ER+ (defined as ER IHC staining \\> 0%) and HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+).\n\nCohort ECNS:\n\n* Patient has histologically or cytologically confirmed stage IIIB (pleural or pericardial effusion) or stage IV NSCLC.\n* Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1\u002FL1 agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who per treating physician are not eligible for approved therapy(ies) (eg, due to intolerance) may be eligible following discussion with the Medical Monitor.\n* Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been previously treated with KRAS-specific therapy are excluded.\n\nCohort ECBF:\n\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Maximum of five prior lines of therapy for advanced\u002Fmetastatic disease.\n  * Recurrence or progression on at least one line of endocrine therapy in the advanced\u002Fmetastatic disease setting.\n  * Prior treatment has included a CDK4\u002F6 inhibitor.\n* Tumor is ER+ (defined as ER IHC staining \\> 0%).\n\nCohort ECBF+A:\n\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Maximum of five prior lines of therapy for advanced\u002Fmetastatic disease.\n  * Recurrence or progression on at least one line of endocrine therapy in the advanced\u002Fmetastatic disease setting.\n* Tumor is ER+ (defined as ER IHC staining \\> 0%) and HER2- (defined as absence of HER2 3+ IHC staining and\u002For absence of FISH+).\n\nCohort ECBT:\n\n* Patient has progressed after treatment with at least one approved anti-HER2 agent and has been administered at least one line of chemotherapy.\n* Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF, EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine therapies.\n\nCohort ECBF-D1:\n\n* Patient has metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit.\n* Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:\n\n  * Minimum of one prior line of therapy for advanced\u002Fmetastatic disease.\n  * Maximum of five prior lines of therapy for advanced\u002Fmetastatic disease.\n  * Recurrence or progression on at least one line of endocrine therapy in the advanced\u002Fmetastatic disease setting.\n  * Prior treatment has included a CDK4\u002F6 inhibitor.\n* Tumor is ER+ (defined as ER IHC staining \\> 0%).\n* Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in situ hybridization.",[149,150],"ADULT","OLDER_ADULT",[152,171,182,190,203,219,227,244,256,267,277,285,300,307],{"facility":153,"status":154,"city":155,"state":156,"zip":157,"country":158,"contacts":159,"geoPoint":168},"University of Southern California","RECRUITING","Los Angeles","California","90033","United States",[160,165],{"name":161,"role":162,"phone":163,"email":164},"Xiomara Menendez","CONTACT","323-409-4638","menendez_x@med.usc.edu",{"name":166,"role":167},"Anthony El-Khoueiry, MD","PRINCIPAL_INVESTIGATOR",{"lat":169,"lon":170},34.05223,-118.24368,{"facility":172,"status":154,"city":155,"state":156,"zip":173,"country":158,"contacts":174,"geoPoint":181},"Valkyrie Clinical Trials","90067",[175,179],{"name":176,"role":162,"phone":177,"email":178},"Chemyn Cortez","559-360-3707","chemyn.cortez@valkyrieclinicaltrials.com",{"name":180,"role":167},"David Berz, MD",{"lat":169,"lon":170},{"facility":183,"status":184,"city":185,"state":156,"zip":186,"country":158,"geoPoint":187},"Hoag Memorial Hospital Presbyterian","COMPLETED","Newport Beach","92663",{"lat":188,"lon":189},33.61891,-117.92895,{"facility":191,"status":154,"city":192,"state":156,"zip":193,"country":158,"contacts":194,"geoPoint":200},"Stanford University","Palo Alto","94304",[195,198],{"name":196,"role":162,"email":197},"Kaushali Thakore-Shah","kthakore@stanford.edu",{"name":199,"role":167},"Jennifer Caswell-Jin, MD",{"lat":201,"lon":202},37.44188,-122.14302,{"facility":204,"status":154,"city":205,"state":206,"zip":207,"country":158,"contacts":208,"geoPoint":216},"START Midwest","Grand Rapids","Michigan","49546",[209,214],{"name":210,"role":162,"phone":211,"phoneExt":212,"email":213},"Abigail Van Kirk","616-954-5550","1824","abigail.vankirk@startmidwest.com",{"name":215,"role":167},"Manish Sharma, MD",{"lat":217,"lon":218},42.96336,-85.66809,{"facility":220,"status":184,"city":221,"state":222,"zip":223,"country":158,"geoPoint":224},"Comprehensive Cancer Centers of Nevada","Las Vegas","Nevada","89169",{"lat":225,"lon":226},36.17497,-115.13722,{"facility":228,"status":154,"city":229,"state":230,"zip":231,"country":158,"contacts":232,"geoPoint":241},"Memorial Sloan Kettering Cancer Center- Monmouth","Middletown","New Jersey","07748",[233,236,239],{"name":234,"role":162,"email":235},"Ezra Rosen","rosene1@mskcc.org",{"name":237,"role":162,"email":238},"Colleen Wenzel","WenzelC1@mskcc.org",{"name":240,"role":167},"Ezra Rosen, MD",{"lat":242,"lon":243},40.39428,-74.11709,{"facility":245,"status":154,"city":246,"state":247,"zip":248,"country":158,"contacts":249,"geoPoint":253},"Memorial Sloan Kettering Cancer Center- Commack","Commack","New York","11725",[250,251,252],{"name":240,"role":162,"email":235},{"name":237,"role":162,"email":238},{"name":240,"role":167},{"lat":254,"lon":255},40.84288,-73.29289,{"facility":257,"status":154,"city":258,"state":247,"zip":259,"country":158,"contacts":260,"geoPoint":264},"Memorial Sloan Kettering Cancer Center- Westchester","Harrison","10604",[261,262,263],{"name":234,"role":162,"email":235},{"name":237,"role":162,"email":238},{"name":240,"role":167},{"lat":265,"lon":266},40.96899,-73.71263,{"facility":268,"status":154,"city":247,"state":247,"zip":269,"country":158,"contacts":270,"geoPoint":274},"Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care","11101",[271,272,273],{"name":240,"role":162,"email":235},{"name":237,"role":162,"email":238},{"name":240,"role":167},{"lat":275,"lon":276},40.71427,-74.00597,{"facility":278,"status":184,"city":279,"state":280,"zip":281,"country":158,"geoPoint":282},"University of Toledo Medical Center","Toledo","Ohio","43614",{"lat":283,"lon":284},41.66394,-83.55521,{"facility":286,"status":154,"city":287,"state":288,"zip":289,"country":158,"contacts":290,"geoPoint":297},"MD Anderson Cancer Center","Houston","Texas","77030",[291,295],{"name":292,"role":162,"phone":293,"email":294},"Amanda Ekert","713-745-8074","ACEckert@mdanderson.org",{"name":296,"role":167},"Funda Meric-Bernstam, MD",{"lat":298,"lon":299},29.76328,-95.36327,{"facility":301,"status":184,"city":302,"state":288,"zip":303,"country":158,"geoPoint":304},"New Experimental Therapeutics of San Antonio - NEXT Oncology","San Antonio","78229",{"lat":305,"lon":306},29.42412,-98.49363,{"facility":308,"status":154,"city":309,"state":310,"zip":311,"country":158,"contacts":312,"geoPoint":319},"Virginia Cancer Specialists","Fairfax","Virginia","22031",[313,317],{"name":314,"role":162,"phone":315,"email":316},"Karina Castillo-Grady","703-280-5390","Karina.CastilloGrady@usoncology.com",{"name":318,"role":167},"Alexander Spira, MD",{"lat":320,"lon":321},38.84622,-77.30637,[323],{"name":324,"role":162,"phone":325,"email":326},"Mark Densel","858-925-8215","clinicaltrials@effector.com",[328],{"name":329,"affiliation":330,"role":331},"Douglas Warner, MD","EFFECTOR Therapeutics, Inc.","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":335,"biomarkers":339},[336,337,338],"Breast Carcinoma","Lung Non-Small Cell Carcinoma","Solid Neoplasm",[340,341],"Cellular proto-oncogene BCL1","Fibroblast Growth Factor Receptor Family",{"nct_id":4,"found":343,"summary":344,"prompt_version":354},true,{"design":345,"status":346,"heading":347,"summary":348,"follow_up":349,"word_count":350,"commitments":351,"compensation":352,"drugs_mentioned":353},"This is an open-label study, meaning you and your doctors will know which treatment you are receiving. It is designed to test different doses and combinations of eFT226 in about 30 participants.","completed","Study of eFT226 for Advanced Solid Tumors","This study is testing a new investigational drug called eFT226, alone and in combination with other approved cancer therapies like sotorasib, fulvestrant, abemaciclib, and trastuzumab. Researchers want to understand how safe eFT226 is, how it moves through the body, and if it can help treat certain advanced solid tumors. The study has already completed its first part, which helped identify the best dose of eFT226. You might be able to join if you are an adult with advanced breast cancer that has not responded to standard treatments or if you cannot tolerate them. The study will look at side effects and how well the treatment works over about 12 months.","The study will measure side effects and the best dose through study completion, which is approximately 12 months.",110,"Not specified in the trial record.","Not stated in the trial record.",[32,42,49,60,66],"v2"]