Ignite Creation Date:
2025-12-24 @ 9:26 PM
Ignite Modification Date:
2026-02-27 @ 1:08 AM
Study NCT ID:
NCT04640532
Status:
UNKNOWN
Last Update Posted:
2022-05-09
First Post:
2020-11-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
KRT-232 in Combination With TL-895 for the Treatment of R/R MF and KRT-232 for the Treatment of JAKi Intolerant MF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055728', 'term': 'Primary Myelofibrosis'}], 'ancestors': [{'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000723723', 'term': 'navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 116}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-11-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-05', 'completionDateStruct': {'date': '2025-07-24', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-05-05', 'studyFirstSubmitDate': '2020-11-17', 'studyFirstSubmitQcDate': '2020-11-17', 'lastUpdatePostDateStruct': {'date': '2022-05-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-11-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-05-11', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Phase 1b - The MTD/MAD and RP2D of TL-895 in combination with KRT-232 in patients with R/R MF (Cohort 1 and Cohort 2)', 'timeFrame': '56 Days', 'description': 'DLTs will be used to establish the MTD. RP2D will be determined by the SRC based on safety data from the combination of TL-895 and KRT-232.'}, {'measure': 'Phase 2 - Spleen response rate for each cohort', 'timeFrame': '24 Weeks', 'description': 'A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 24'}], 'secondaryOutcomes': [{'measure': 'Total Symptom Score (TSS)', 'timeFrame': '24 Weeks', 'description': 'The change in TSS based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Relapsed/Refractory Myelofibrosis', 'Janus associated Kinase Inhibitor-Intolerant Myelofibrosis', 'MDM2', 'navtemadlin'], 'conditions': ['Myelofibrosis', 'Post-PV MF', 'Post-ET Myelofibrosis', 'Primary Myelofibrosis']}, 'descriptionModule': {'briefSummary': 'This study evaluates KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.', 'detailedDescription': 'Cohorts 1 and 2 will undergo dose finding and dose expansion. Eligible patients will be randomly assigned to an open cohort, either Cohort 1 or Cohort 2. Cohort 3 will be conducted as a dose expansion, independent of Cohorts 1 and 2.\n\nCohort 1 will follow a 3+3 dose escalation design to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of TL-895 administered QD in combination with KRT-232. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.\n\nCohort 2 will follow a 3+3 dose escalation design to determine the MTD/MAD and recommended RP2D of TL-895 administered BID in combination with KRT-232. An SRC will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.\n\nCohort 3 will be conducted a 2-stage design. In stage 1, enrollment will continue until 15 evaluable patients have been enrolled. An SRC will review the data during the study and if there are ≥4 responders based on the futility criteria and safety data from Stage 1, Cohort 3 expansion will commence. If there are ≤3 patients responding to therapy, Cohort 3 will be terminated. Once expansion criteria have been met, Cohort 3 will be expanded to a total of 46 evaluable patients for Stage 2 analyses.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, (WHO 2016)\n* ECOG ≤ 2\n* Cohort 1 and Cohort 2: R/R following JAK inhibitor treatment\n* Cohort 3: patients who are intolerant to JAK inhibitor treatment\n\nExclusion Criteria:\n\n* Prior treatment with MDM2 inhibitors or p53-directed therapies\n* Prior treatment with a BCR-ABL, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR), bromodomain and extraterminal domain (BET), histone deacetylase (HDAC), or spleen tyrosine kinase (Syk) inhibitor\n* Prior splenectomy\n* Splenic irradiation within 3 months prior to the first dose of study treatment\n* Clinically significant thrombosis within 3 months of screening\n* Grade 2 or higher QTc prolongation'}, 'identificationModule': {'nctId': 'NCT04640532', 'briefTitle': 'KRT-232 in Combination With TL-895 for the Treatment of R/R MF and KRT-232 for the Treatment of JAKi Intolerant MF', 'organization': {'class': 'INDUSTRY', 'fullName': 'Kartos Therapeutics, Inc.'}, 'officialTitle': 'An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.', 'orgStudyIdInfo': {'id': 'KRT-232-113'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1 (R/R MF), Dose Level 1', 'description': 'TL-895 at 200 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle.\n\nKRT-232 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.', 'interventionNames': ['Drug: KRT-232', 'Drug: TL-895']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 1 (R/R MF), Dose Level 2', 'description': 'TL-895 at 300 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle.\n\nKRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.', 'interventionNames': ['Drug: KRT-232', 'Drug: TL-895']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2 (R/R MF), Dose Level 1', 'description': 'TL-895 at 100 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle.\n\nKRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.', 'interventionNames': ['Drug: KRT-232', 'Drug: TL-895']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2 (R/R MF), Dose Level 2', 'description': 'TL-895 at 150 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle.\n\nKRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.', 'interventionNames': ['Drug: KRT-232', 'Drug: TL-895']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 3 (JAKi Intolerant MF)', 'description': 'KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.', 'interventionNames': ['Drug: KRT-232']}], 'interventions': [{'name': 'KRT-232', 'type': 'DRUG', 'description': 'KRT-232, administered by mouth', 'armGroupLabels': ['Cohort 1 (R/R MF), Dose Level 1', 'Cohort 1 (R/R MF), Dose Level 2', 'Cohort 2 (R/R MF), Dose Level 1', 'Cohort 2 (R/R MF), Dose Level 2', 'Cohort 3 (JAKi Intolerant MF)']}, {'name': 'TL-895', 'type': 'DRUG', 'description': 'TL-895, administered by mouth', 'armGroupLabels': ['Cohort 1 (R/R MF), Dose Level 1', 'Cohort 1 (R/R MF), Dose Level 2', 'Cohort 2 (R/R MF), Dose Level 1', 'Cohort 2 (R/R MF), Dose Level 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35233', 'city': 'Birmingham', 'state': 'Alabama', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '90603', 'city': 'Whittier', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'The Oncology Institute of Hope', 'geoPoint': {'lat': 33.97918, 'lon': -118.03284}}, {'zip': '32024', 'city': 'Lake City', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Lake City Cancer Center', 'geoPoint': {'lat': 30.18968, 'lon': -82.63929}}, {'zip': '61801', 'city': 'Urbana', 'state': 'Illinois', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Carle Cancer Center', 'geoPoint': {'lat': 40.11059, 'lon': -88.20727}}, {'zip': '07024', 'city': 'Fort Lee', 'state': 'New Jersey', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Columbia University Medical Center', 'geoPoint': {'lat': 40.85093, 'lon': -73.97014}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Memorial Sloan Kettering Cancer Center (MSKCC)', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '8700', 'city': 'Leoben', 'status': 'RECRUITING', 'country': 'Austria', 'facility': 'LKH Hochsteiermark', 'geoPoint': {'lat': 47.3765, 'lon': 15.09144}}, {'zip': '1090', 'city': 'Vienna', 'status': 'RECRUITING', 'country': 'Austria', 'facility': 'Meduni Wien, Univ. Klinik für Innere Medizin I', 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': '5800', 'city': 'Pleven', 'status': 'RECRUITING', 'country': 'Bulgaria', 'facility': 'University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven', 'geoPoint': {'lat': 43.41791, 'lon': 24.61666}}, {'zip': '4002', 'city': 'Plovdiv', 'status': 'RECRUITING', 'country': 'Bulgaria', 'facility': 'University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv', 'geoPoint': {'lat': 42.15387, 'lon': 24.75001}}, {'zip': '1756', 'city': 'Sofia', 'status': 'RECRUITING', 'country': 'Bulgaria', 'facility': 'Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia', 'geoPoint': {'lat': 42.69751, 'lon': 23.32415}}, {'zip': '80054', 'city': 'Amiens', 'status': 'RECRUITING', 'country': 'France', 'facility': 'Chu Amiens Picardie Site Sud', 'geoPoint': {'lat': 49.9, 'lon': 2.3}}, {'zip': '87042', 'city': 'Limoges', 'status': 'RECRUITING', 'country': 'France', 'facility': 'CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire', 'geoPoint': {'lat': 45.83362, 'lon': 1.24759}}, {'zip': '44093', 'city': 'Nantes', 'status': 'RECRUITING', 'country': 'France', 'facility': 'CHU Nantes - Hôtel Dieu', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}, {'zip': '06200', 'city': 'Nice', 'status': 'RECRUITING', 'country': 'France', 'facility': 'CHU de Nice Hospital', 'geoPoint': {'lat': 43.70313, 'lon': 7.26608}}, {'zip': '75475', 'city': 'Paris', 'status': 'RECRUITING', 'country': 'France', 'facility': 'Hôpital Saint Louis', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '63310', 'city': 'Pierre-Bénite', 'status': 'RECRUITING', 'country': 'France', 'facility': 'Centre Hospitalier Lyon Sud', 'geoPoint': {'lat': 45.70359, 'lon': 4.82424}}, {'zip': '06120', 'city': 'Halle', 'status': 'RECRUITING', 'country': 'Germany', 'facility': 'University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology', 'geoPoint': {'lat': 51.48158, 'lon': 11.97947}}, {'zip': '35043', 'city': 'Marburg', 'status': 'RECRUITING', 'country': 'Germany', 'facility': 'University Hospital Marburg, Department of Hematology, Oncology and Immunology', 'geoPoint': {'lat': 50.80904, 'lon': 8.77069}}, {'zip': 'H-7400', 'city': 'Kaposvár', 'status': 'RECRUITING', 'country': 'Hungary', 'facility': 'Moritz Kaposi General Hospital, Department of Hematology', 'geoPoint': {'lat': 46.36667, 'lon': 17.8}}, {'zip': 'H-4400', 'city': 'Nyíregyháza', 'status': 'RECRUITING', 'country': 'Hungary', 'facility': 'Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology', 'geoPoint': {'lat': 47.95539, 'lon': 21.71671}}, {'zip': 'H-7624', 'city': 'Pécs', 'status': 'RECRUITING', 'country': 'Hungary', 'facility': 'Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology', 'geoPoint': {'lat': 46.07617, 'lon': 18.22814}}, {'zip': 'H-8000', 'city': 'Székesfehérvár', 'status': 'RECRUITING', 'country': 'Hungary', 'facility': 'Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology', 'geoPoint': {'lat': 47.18995, 'lon': 18.41034}}, {'zip': '40138', 'city': 'Bologna', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Polyclinic S. Orsola-Malpighi', 'geoPoint': {'lat': 44.49381, 'lon': 11.33875}}, {'zip': '25123', 'city': 'Brescia', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'ASST Spedali Civili di Brescia', 'geoPoint': {'lat': 45.53558, 'lon': 10.21472}}, {'zip': '50134', 'city': 'Florence', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Careggi University Hospital', 'geoPoint': {'lat': 43.77925, 'lon': 11.24626}}, {'zip': '71013', 'city': 'Foggia', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology', 'geoPoint': {'lat': 41.45845, 'lon': 15.55188}}, {'zip': '48121', 'city': 'Ravenna', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Hospital of Ravenna, Operative Unit of Hematology', 'geoPoint': {'lat': 44.41344, 'lon': 12.20121}}, {'zip': '85-168', 'city': 'Bydgoszcz', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology', 'geoPoint': {'lat': 53.1235, 'lon': 18.00762}}, {'zip': '40-519', 'city': 'Katowice', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Pratia Onkologia Katowice', 'geoPoint': {'lat': 50.2597, 'lon': 19.02173}}, {'zip': '35-055', 'city': 'Rzeszów', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology', 'geoPoint': {'lat': 50.04132, 'lon': 21.99901}}, {'zip': '76-200', 'city': 'Słupsk', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology', 'geoPoint': {'lat': 54.46405, 'lon': 17.02872}}, {'zip': '87-100', 'city': 'Torun', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka', 'geoPoint': {'lat': 53.01375, 'lon': 18.59814}}, {'zip': '11000', 'city': 'Belgrade', 'status': 'RECRUITING', 'country': 'Serbia', 'facility': 'Clinical Center of Serbia', 'geoPoint': {'lat': 44.80401, 'lon': 20.46513}}, {'zip': '21000', 'city': 'Novi Sad', 'status': 'RECRUITING', 'country': 'Serbia', 'facility': 'Clinical Center of Vojvodina', 'geoPoint': {'lat': 45.25167, 'lon': 19.83694}}, {'zip': '08003', 'city': 'Barcelona', 'status': 'RECRUITING', 'country': 'Spain', 'facility': 'Hematologia Clínica', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '37007', 'city': 'Salamanca', 'status': 'RECRUITING', 'country': 'Spain', 'facility': 'University Clinical Hospital of Salamanca, Department of Hematology', 'geoPoint': {'lat': 40.96882, 'lon': -5.66388}}], 'centralContacts': [{'name': 'John Mei', 'role': 'CONTACT', 'email': 'jmei@kartosthera.com', 'phone': '650-542-0136'}, {'name': 'Irene Dea', 'role': 'CONTACT', 'email': 'idea@kartosthera.com', 'phone': '(650) 839-7341'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kartos Therapeutics, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Telios Pharma, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}