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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04669067
• Other study ID #: TL-895-203
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 31, 2021
• Est. completion date: November 2025

Study information

• Verified date: February 2023
• Source: Telios Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
• KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.

Locations

Country	Name	City	State
Australia	University of Sunshine Coast-Sippy Downs	Sippy Downs
Australia	Westmead Hospital	Sydney
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Austria	Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology	Vienna
France	Claude Huriez Hospital	Lille
France	South Lyon Hospital Center	Lyon
France	Paoli-Calmettes Institute	Marseille
France	University Hospital of Nantes	Nantes
France	Hospital Center Universitaire De Nice	Nice
France	Saint-Louis Hospital	Paris
Germany	University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine	Essen
Germany	University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology	Halle	Sachsen-Anhalt
Germany	University Hospital Hamburg-Eppendorf, Department of Internal Medicine II	Hamburg
Germany	Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation	Hannover
Germany	University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology	Jena
Italy	University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic	Ancona
Italy	Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology	Bologna
Italy	Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology	Meldola
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Hospital, Department of Hemato-Oncology	Seoul
Spain	University Hospital Germans Trias i Pujol, Department of Clinical Hematology	Badalona
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology	Valencia
Spain	Hospital Universitario y Politécnico de La Fe	València
United States	Georgia Cancer Center	Augusta	Georgia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center, Division of Hematology Oncology and Cell Therapy	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	UT Southwestern Medical Center, Harold C. Simmons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Keck School of Medicine	Los Angeles	California
United States	Weill Cornell Medical College	New York	New York
United States	University of California, Irvine Medical Center	Orange	California
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Telios Pharma, Inc.	Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Germany,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	13 months
Primary	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).	41 months
Secondary	Key Secondary Objective: To determine the overall response rate (ORR)	The proportion of subjects who achieve PR or better.	41 months
Secondary	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.	41 months