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

NCT ID: NCT04640532

Last Updated: 2022-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-17

Study Completion Date

2025-07-24

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Myelofibrosis Post-PV MF Post-ET Myelofibrosis Primary Myelofibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232, administered by mouth

TL-895

Intervention Type DRUG

TL-895, administered by mouth

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.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232, administered by mouth

TL-895

Intervention Type DRUG

TL-895, administered by mouth

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.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232, administered by mouth

TL-895

Intervention Type DRUG

TL-895, administered by mouth

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.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232, administered by mouth

TL-895

Intervention Type DRUG

TL-895, administered by mouth

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.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232, administered by mouth

Interventions

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KRT-232

KRT-232, administered by mouth

Intervention Type DRUG

TL-895

TL-895, administered by mouth

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Telios Pharma, Inc.

INDUSTRY

Sponsor Role collaborator

Kartos Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology

Birmingham, Alabama, United States

Site Status RECRUITING

The Oncology Institute of Hope

Whittier, California, United States

Site Status RECRUITING

Lake City Cancer Center

Lake City, Florida, United States

Site Status RECRUITING

Carle Cancer Center

Urbana, Illinois, United States

Site Status RECRUITING

Columbia University Medical Center

Fort Lee, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Site Status RECRUITING

LKH Hochsteiermark

Leoben, , Austria

Site Status RECRUITING

Meduni Wien, Univ. Klinik für Innere Medizin I

Vienna, , Austria

Site Status RECRUITING

University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven

Pleven, , Bulgaria

Site Status RECRUITING

University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv

Plovdiv, , Bulgaria

Site Status RECRUITING

Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia

Sofia, , Bulgaria

Site Status RECRUITING

Chu Amiens Picardie Site Sud

Amiens, , France

Site Status RECRUITING

CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire

Limoges, , France

Site Status RECRUITING

CHU Nantes - Hôtel Dieu

Nantes, , France

Site Status RECRUITING

CHU de Nice Hospital

Nice, , France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology

Halle, , Germany

Site Status RECRUITING

University Hospital Marburg, Department of Hematology, Oncology and Immunology

Marburg, , Germany

Site Status RECRUITING

Moritz Kaposi General Hospital, Department of Hematology

Kaposvár, , Hungary

Site Status RECRUITING

Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology

Nyíregyháza, , Hungary

Site Status RECRUITING

Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology

Pécs, , Hungary

Site Status RECRUITING

Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology

Székesfehérvár, , Hungary

Site Status RECRUITING

Polyclinic S. Orsola-Malpighi

Bologna, , Italy

Site Status RECRUITING

ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status RECRUITING

Careggi University Hospital

Florence, , Italy

Site Status RECRUITING

Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology

Foggia, , Italy

Site Status RECRUITING

Hospital of Ravenna, Operative Unit of Hematology

Ravenna, , Italy

Site Status RECRUITING

Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology

Bydgoszcz, , Poland

Site Status RECRUITING

Pratia Onkologia Katowice

Katowice, , Poland

Site Status RECRUITING

Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology

Rzeszów, , Poland

Site Status RECRUITING

Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology

Słupsk, , Poland

Site Status RECRUITING

Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka

Torun, , Poland

Site Status RECRUITING

Clinical Center of Serbia

Belgrade, , Serbia

Site Status RECRUITING

Clinical Center of Vojvodina

Novi Sad, , Serbia

Site Status RECRUITING

Hematologia Clínica

Barcelona, , Spain

Site Status RECRUITING

University Clinical Hospital of Salamanca, Department of Hematology

Salamanca, , Spain

Site Status RECRUITING

Countries

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United States Austria Bulgaria France Germany Hungary Italy Poland Serbia Spain

Central Contacts

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John Mei

Role: CONTACT

650-542-0136

Irene Dea

Role: CONTACT

(650) 839-7341

Other Identifiers

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KRT-232-113

Identifier Type: -

Identifier Source: org_study_id

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