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NCT04640532 Clinical Trial

KRT-232 in Combination With TL-895 for the Treatment of R/R MF and KRT-232 for the Treatment of JAKi Intolerant MF

Myelofibrosis Clinical Trial

Official title:
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.

Clinical Trial Details — Status: Recruiting

Administrative data
NCT number NCT04640532
Other study ID # KRT-232-113
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date November 17, 2020
Est. completion date July 24, 2025

Study information
Verified date May 2022
Source Kartos Therapeutics, Inc.
Contact John Mei
Phone 650-542-0136
Email jmei@kartosthera.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.

Description:

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. Cohort 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. Cohort 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. Cohort 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.

Recruitment information / eligibility
Status Recruiting
Enrollment 116
Est. completion date July 24, 2025
Est. primary completion date May 11, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, (WHO 2016) - ECOG = 2 - Cohort 1 and Cohort 2: R/R following JAK inhibitor treatment - Cohort 3: patients who are intolerant to JAK inhibitor treatment Exclusion Criteria: - Prior treatment with MDM2 inhibitors or p53-directed therapies - 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 - Prior splenectomy - Splenic irradiation within 3 months prior to the first dose of study treatment - Clinically significant thrombosis within 3 months of screening - Grade 2 or higher QTc prolongation

Study Design

Related Conditions & MeSH terms

Intervention

Drug:
• KRT-232
KRT-232, administered by mouth
• TL-895
TL-895, administered by mouth

Locations
Country Name City State
Austria LKH Hochsteiermark Leoben
Austria Meduni Wien, Univ. Klinik für Innere Medizin I Wien
Bulgaria University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven Pleven
Bulgaria University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv Plovdiv
Bulgaria Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia Sofia
France Chu Amiens Picardie Site Sud Amiens
France CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire Limoges
France CHU Nantes - Hôtel Dieu Nantes
France CHU de Nice Hospital Nice
France Hôpital Saint Louis Paris
France Centre Hospitalier Lyon Sud Pierre-Bénite
Germany University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology Halle
Germany University Hospital Marburg, Department of Hematology, Oncology and Immunology Marburg
Hungary Moritz Kaposi General Hospital, Department of Hematology Kaposvár
Hungary Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology Nyíregyháza
Hungary Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology Pécs
Hungary Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology Székesfehérvár
Italy Polyclinic S. Orsola-Malpighi Bologna
Italy ASST Spedali Civili di Brescia Brescia
Italy Careggi University Hospital Florence
Italy Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology Foggia
Italy Hospital of Ravenna, Operative Unit of Hematology Ravenna
Poland Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology Bydgoszcz
Poland Pratia Onkologia Katowice Katowice
Poland Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology Rzeszów
Poland Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology Slupsk
Poland Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka Torun
Serbia Clinical Center of Serbia Belgrade
Serbia Clinical Center of Vojvodina Novi Sad
Spain Hematologia Clínica Barcelona
Spain University Clinical Hospital of Salamanca, Department of Hematology Salamanca
United States University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology Birmingham Alabama
United States Columbia University Medical Center Fort Lee New Jersey
United States Lake City Cancer Center Lake City Florida
United States Memorial Sloan Kettering Cancer Center (MSKCC) New York New York
United States Carle Cancer Center Urbana Illinois
United States The Oncology Institute of Hope Whittier California

Sponsors (2)
Lead Sponsor Collaborator
Kartos Therapeutics, Inc. Telios Pharma, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  France,  Germany,  Hungary,  Italy,  Poland,  Serbia,  Spain, 

Outcome
Type Measure Description Time frame Safety issue
Primary 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) 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. 56 Days
Primary Phase 2 - Spleen response rate for each cohort A reduction in spleen volume as assessed by MRI (or CT) = 35% from baseline at Week 24 24 Weeks
Secondary Total Symptom Score (TSS) The change in TSS based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) 24 Weeks
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