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

May 5, 2022 updated by: Kartos Therapeutics, Inc.

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

116

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Austria
      • Leoben, Austria, 8700
        • Recruiting
        • LKH Hochsteiermark
      • Wien, Austria, 1090
        • Recruiting
        • Meduni Wien, Univ. Klinik für Innere Medizin I
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Recruiting
        • University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven
      • Plovdiv, Bulgaria, 4002
        • Recruiting
        • University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv
      • Sofia, Bulgaria, 1756
        • Recruiting
        • Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia
  • France
      • Amiens, France, 80054
        • Recruiting
        • CHU Amiens Picardie Site Sud
      • Limoges, France, 87042
        • Recruiting
        • CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire
      • Nantes, France, 44093
        • Recruiting
        • CHU NANTES - Hôtel Dieu
      • Nice, France, 06200
        • Recruiting
        • CHU de Nice Hospital
      • Paris, France, 75475
        • Recruiting
        • Hopital Saint Louis
      • Pierre-Bénite, France, 63310
        • Recruiting
        • Centre Hospitalier Lyon Sud
  • Germany
      • Halle, Germany, 06120
        • Recruiting
        • University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
      • Marburg, Germany, 35043
        • Recruiting
        • University Hospital Marburg, Department of Hematology, Oncology and Immunology
  • Hungary
      • Kaposvár, Hungary, H-7400
        • Recruiting
        • Moritz Kaposi General Hospital, Department of Hematology
      • Nyíregyháza, Hungary, H-4400
        • Recruiting
        • Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology
      • Pécs, Hungary, H-7624
        • Recruiting
        • Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology
      • Székesfehérvár, Hungary, H-8000
        • Recruiting
        • Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Polyclinic S. Orsola-Malpighi
      • Brescia, Italy, 25123
        • Recruiting
        • Asst Spedali Civili Di Brescia
      • Florence, Italy, 50134
        • Recruiting
        • Careggi University Hospital
      • Foggia, Italy, 71013
        • Recruiting
        • Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology
      • Ravenna, Italy, 48121
        • Recruiting
        • Hospital of Ravenna, Operative Unit of Hematology
  • Poland
      • Bydgoszcz, Poland, 85-168
        • Recruiting
        • Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology
      • Katowice, Poland, 40-519
        • Recruiting
        • Pratia Onkologia Katowice
      • Rzeszów, Poland, 35-055
        • Recruiting
        • Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology
      • Słupsk, Poland, 76-200
        • Recruiting
        • Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology
      • Toruń, Poland, 87-100
        • Recruiting
        • Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka
  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinical Center of Serbia
      • Novi Sad, Serbia, 21000
        • Recruiting
        • Clinical Center of Vojvodina
  • Spain
      • Barcelona, Spain, 08003
        • Recruiting
        • Hematologia Clínica
      • Salamanca, Spain, 37007
        • Recruiting
        • University Clinical Hospital of Salamanca, Department of Hematology
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology
    • California
      • Whittier, California, United States, 90603
        • Recruiting
        • The Oncology Institute of Hope
    • Florida
      • Lake City, Florida, United States, 32024
        • Recruiting
        • Lake City Cancer Center
    • Illinois
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
    • New Jersey
      • Fort Lee, New Jersey, United States, 07024
        • Recruiting
        • Columbia University Medical Center
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center (MSKCC)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 1 (R/R MF), Dose Level 1

TL-895 at 200 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle.

KRT-232 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
Drug: KRT-232
KRT-232, administered by mouth
Drug: TL-895
TL-895, administered by mouth
EXPERIMENTAL: Cohort 1 (R/R MF), Dose Level 2

TL-895 at 300 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle.

KRT-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.
Drug: KRT-232
KRT-232, administered by mouth
Drug: TL-895
TL-895, administered by mouth
EXPERIMENTAL: Cohort 2 (R/R MF), Dose Level 1

TL-895 at 100 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle.

KRT-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.
Drug: KRT-232
KRT-232, administered by mouth
Drug: TL-895
TL-895, administered by mouth
EXPERIMENTAL: Cohort 2 (R/R MF), Dose Level 2

TL-895 at 150 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle.

KRT-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.
Drug: KRT-232
KRT-232, administered by mouth
Drug: TL-895
TL-895, administered by mouth
EXPERIMENTAL: Cohort 3 (JAKi Intolerant MF)
KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Drug: KRT-232
KRT-232, administered by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 56 Days
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
Phase 2 - Spleen response rate for each cohort
Time Frame: 24 Weeks
A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 24
24 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Symptom Score (TSS)
Time Frame: 24 Weeks
The change in TSS based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Collaborators

Telios Pharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 17, 2020

Primary Completion (ANTICIPATED)

May 11, 2022

Study Completion (ANTICIPATED)

July 24, 2025

Study Registration Dates

First Submitted

November 17, 2020

First Submitted That Met QC Criteria

November 17, 2020

First Posted (ACTUAL)

November 23, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 9, 2022

Last Update Submitted That Met QC Criteria

May 5, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-113

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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