TL-895 and KRT-232 Study in Acute Myeloid Leukemia

February 15, 2023 updated by: Telios Pharma, Inc.

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined With KRT-232 in Patients With Relapsed/Refractory (R/R) FLT3+ Acute Myeloid Leukemia (AML)

This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with navtemadlin (KRT-232), a novel oral small molecule inhibitor of MDM2 for the treatment of adults with FLT3 mutated Acute Myeloid Leukemia. Participants must be relapsed/refractory (e.g., having failed prior therapy) to be eligible for this study.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

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 Contact Backup

Study Locations

  • Australia
      • Sippy Downs, Australia, 4556
        • University of Sunshine Coast-Sippy Downs
      • Sydney, Australia, 2145
        • Westmead Hospital
  • Austria
      • Linz, Austria, 4020
        • Ordensklinikum Linz Gmbh Elisabethinen
      • Vienna, Austria, 1090
        • Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
  • France
      • Lille, France, 59037
        • Claude Huriez Hospital
      • Lyon, France, 48178
        • South Lyon Hospital Center
      • Marseille, France, 13009
        • Paoli-Calmettes Institute
      • Nantes, France, 44000
        • University Hospital of Nantes
      • Nice, France, 06000
        • Hospital Center Universitaire De Nice
      • Paris, France, 75010
        • Saint-Louis Hospital
  • Germany
      • Essen, Germany, 45147
        • University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
      • Hamburg, Germany, 20246
        • University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
      • Hannover, Germany, 30625
        • Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
      • Jena, Germany, 07747
        • University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06120
        • University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
  • Italy
      • Ancona, Italy, 60126
        • University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic
      • Bologna, Italy, 40138
        • Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology
      • Meldola, Italy, 47014
        • Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
  • Korea, Republic of
      • Incheon, Korea, Republic of, 21565
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital, Department of Hemato-Oncology
  • Spain
      • Badalona, Spain, 08916
        • University Hospital Germans Trias i Pujol, Department of Clinical Hematology
      • Barcelona, Spain, 08035
        • University Hospital Vall d'Hebron
      • Valencia, Spain, 46010
        • University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
      • València, Spain, 46026
        • Hospital Universitario y Politécnico de La Fe
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Keck School Of Medicine
      • Orange, California, United States, 92868
        • University of California, Irvine Medical Center
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center, Harold C. Simmons Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

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:

  • TP53 wildtype AML
  • Relapsed/Refractory to at least one prior therapy, one of which must have included a FLT-3 inhibitor
  • FLT3 mutation (FLT3-TKD or FLT3-ITD)
  • ECOG 0-2
  • Adequate hematologic, hepatic, and renal functions

Exclusion Criteria:

  • AML subtype 3
  • Prior treatment with MDM2 antagonist therapies
  • Eligible for HSCT

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1b - Dose Level 1
KRT-232 240mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Experimental: Phase 1b - Dose Level 2
KRT-232 300mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Experimental: Phase 1b - Dose Level 3

Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 150 mg BID continuously for the first 28-day cycle

Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 150 mg BID continuously for each 28-day cycle.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Experimental: Phase 1b - Dose Level 4

Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 300 mg BID continuously for the first 28-day cycle.

Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 300 mg BID continuously for each 28-day cycle.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Experimental: Phase 1b - Dose Level 5

Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 450 mg BID continuously for the first 28-day cycle.

Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 450 mg BID continuously for each 28-day cycle.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Experimental: Phase 2 - Dose Expansion
Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
Time Frame: 13 months
Dose limiting toxicities will be used to established the MTD/MAD of TL-895 combined with KRT-232. The Safety Review Committee (SRC) will determine the RP2D based on safety data of the combination of TL-895 and KRT-232.
13 months
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
Time Frame: 41 months
The proportion of subjects who achieved CR or CRh as their best response based on the Modified 2017 European LeukemiaNet (ELN) Response Criteria (Appendix 4).
41 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Key Secondary Objective: To determine the overall response rate (ORR)
Time Frame: 41 months
The proportion of subjects who achieve PR or better.
41 months
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Time Frame: 41 months
Median DOR (Kaplan-Meier estimate) defined as the time from first observation of CR/CRh to relapse or death from any cause, whichever occurs first. Subjects with MLFS by bone marrow biopsy performed earlier in the course of therapy who convert to CR or CRh do not require a separate bone marrow aspirate at the time of CR or CRh to document this.
41 months

Collaborators and Investigators

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

Sponsor

Telios Pharma, Inc.

Collaborators

Kartos Therapeutics, 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)

March 31, 2021

Primary Completion (Anticipated)

November 1, 2024

Study Completion (Anticipated)

November 1, 2025

Study Registration Dates

First Submitted

December 2, 2020

First Submitted That Met QC Criteria

December 10, 2020

First Posted (Actual)

December 16, 2020

Study Record Updates

Last Update Posted (Actual)

February 17, 2023

Last Update Submitted That Met QC Criteria

February 15, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TL-895-203

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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