search
Back to results

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

Primary Purpose

Acute Myeloid Leukemia

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TL-895
KRT-232
Sponsored by
Telios Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, TP53, FLT3+, Navtemadlin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Keck School of Medicine
  • University of California, Irvine Medical Center
  • Georgia Cancer Center
  • Northwestern Memorial Hospital
  • Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
  • Karmanos Cancer Institute
  • Weill Cornell Medical College
  • University of Cincinnati
  • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
  • UT Southwestern Medical Center, Harold C. Simmons Cancer Center
  • Seattle Cancer Care Alliance
  • University of Sunshine Coast-Sippy Downs
  • Westmead Hospital
  • Ordensklinikum Linz GmbH Elisabethinen
  • Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
  • Claude Huriez Hospital
  • South Lyon Hospital Center
  • Paoli-Calmettes Institute
  • University Hospital of Nantes
  • Hospital Center Universitaire De Nice
  • Saint-Louis Hospital
  • University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
  • University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
  • University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
  • Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
  • University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
  • University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic
  • Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology
  • Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
  • Gachon University Gil Medical Center
  • Seoul National University Hospital, Department of Hemato-Oncology
  • University Hospital Germans Trias i Pujol, Department of Clinical Hematology
  • University Hospital Vall d'Hebron
  • University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
  • Hospital Universitario y Politécnico de La Fe

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1b - Dose Level 1

Phase 1b - Dose Level 2

Phase 1b - Dose Level 3

Phase 1b - Dose Level 4

Phase 1b - Dose Level 5

Phase 2 - Dose Expansion

Arm Description

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.

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.

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.

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.

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.

Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b.

Outcomes

Primary Outcome Measures

Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
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.
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
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).

Secondary Outcome Measures

Key Secondary Objective: To determine the overall response rate (ORR)
The proportion of subjects who achieve PR or better.
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
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.

Full Information

First Posted
December 2, 2020
Last Updated
February 15, 2023
Sponsor
Telios Pharma, Inc.
Collaborators
Kartos Therapeutics, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT04669067
Brief Title
TL-895 and KRT-232 Study in Acute Myeloid Leukemia
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telios Pharma, Inc.
Collaborators
Kartos Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML, TP53, FLT3+, Navtemadlin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b - Dose Level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b - Dose Level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b - Dose Level 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b - Dose Level 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b - Dose Level 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 - Dose Expansion
Arm Type
Experimental
Arm Description
Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b.
Intervention Type
Drug
Intervention Name(s)
TL-895
Intervention Description
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Primary Outcome Measure Information:
Title
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
Description
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.
Time Frame
13 months
Title
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
Description
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).
Time Frame
41 months
Secondary Outcome Measure Information:
Title
Key Secondary Objective: To determine the overall response rate (ORR)
Description
The proportion of subjects who achieve PR or better.
Time Frame
41 months
Title
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Description
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.
Time Frame
41 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Keck School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California, Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Georgia Cancer Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
UT Southwestern Medical Center, Harold C. Simmons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Sunshine Coast-Sippy Downs
City
Sippy Downs
ZIP/Postal Code
4556
Country
Australia
Facility Name
Westmead Hospital
City
Sydney
ZIP/Postal Code
2145
Country
Australia
Facility Name
Ordensklinikum Linz GmbH Elisabethinen
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Claude Huriez Hospital
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
South Lyon Hospital Center
City
Lyon
ZIP/Postal Code
48178
Country
France
Facility Name
Paoli-Calmettes Institute
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
University Hospital of Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Name
Hospital Center Universitaire De Nice
City
Nice
ZIP/Postal Code
06000
Country
France
Facility Name
Saint-Louis Hospital
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
City
Halle
State/Province
Sachsen-Anhalt
ZIP/Postal Code
06120
Country
Germany
Facility Name
University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic
City
Ancona
ZIP/Postal Code
60126
Country
Italy
Facility Name
Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
City
Meldola
ZIP/Postal Code
47014
Country
Italy
Facility Name
Gachon University Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
Seoul National University Hospital, Department of Hemato-Oncology
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
University Hospital Germans Trias i Pujol, Department of Clinical Hematology
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
University Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hospital Universitario y Politécnico de La Fe
City
València
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs