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

NCT04669067 | Unknown Phase 1 FDA Drug

• 1 other identifier: TL-895-203
• Study Type: interventional
• Target: 18
• Locations: 7 countries
• Sites: 33

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML; TP53; FLT3+; Navtemadlin

Outcome Measures

Primary Outcomes (2)

• 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 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 Outcomes (2)

• Key Secondary Objective: To determine the overall response rate (ORR)

  41 months

• Key Secondary Objective: To determine the duration of CR/CRh response (DOR)

  41 months

Study Arms (6)

Phase 1b - Dose Level 1

EXPERIMENTAL

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; Drug: KRT-232

Phase 1b - Dose Level 2

EXPERIMENTAL

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; Drug: KRT-232

Phase 1b - Dose Level 3

EXPERIMENTAL

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; Drug: KRT-232

Phase 1b - Dose Level 4

EXPERIMENTAL

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; Drug: KRT-232

Phase 1b - Dose Level 5

EXPERIMENTAL

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; Drug: KRT-232

Phase 2 - Dose Expansion

EXPERIMENTAL

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

Drug: TL-895; Drug: KRT-232

Interventions

TL-895 DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

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

KRT-232 DRUG

KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Telios Pharma, Inc.: lead
• Kartos Therapeutics, Inc.: collaborator

Study Sites (35)

Keck School of Medicine

Los Angeles, California, 90033, United States

Location

University of California, Irvine Medical Center

Orange, California, 92868, United States

Location

Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center, Division of Hematology Oncology and Cell Therapy

Chicago, Illinois, 60612, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

Philadelphia, Pennsylvania, 19107, United States

Location

UT Southwestern Medical Center, Harold C. Simmons Cancer Center

Dallas, Texas, 75390, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Sunshine Coast-Sippy Downs

Sippy Downs, 4556, Australia

Location

Westmead Hospital

Sydney, 2145, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

Location

Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology

Vienna, 1090, Austria

Location

Claude Huriez Hospital

Lille, 59037, France

Location

South Lyon Hospital Center

Lyon, 48178, France

Location

Paoli-Calmettes Institute

Marseille, 13009, France

Location

University Hospital of Nantes

Nantes, 44000, France

Location

Hospital Center Universitaire De Nice

Nice, 06000, France

Location

Saint-Louis Hospital

Paris, 75010, France

Location

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

Halle, Saxony-Anhalt, 06120, Germany

Location

University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine

Essen, 45147, Germany

Location

University Hospital Hamburg-Eppendorf, Department of Internal Medicine II

Hamburg, 20246, Germany

Location

Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation

Hanover, 30625, Germany

Location

University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology

Jena, 07747, Germany

Location

University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic

Ancona, 60126, Italy

Location

Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology

Bologna, 40138, Italy

Location

Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology

Meldola, 47014, Italy

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital, Department of Hemato-Oncology

Seoul, 03080, South Korea

Location

University Hospital Germans Trias i Pujol, Department of Clinical Hematology

Badalona, 08916, Spain

Location

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology

Valencia, 46010, Spain

Location

Hospital Universitario y Politécnico de La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 16, 2020
• Study Start: March 31, 2021
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2025
• Last Updated: February 17, 2023

Record last verified: 2023-02

Locations

DE (5); ES (4); AU (2); IT (3); KR (2); US (11); FR (6)