TL-895 and KRT-232 Study in Acute Myeloid Leukemia
- Registration Number
- NCT04669067
- Lead Sponsor
- Telios Pharma, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 18
- 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
- AML subtype 3
- Prior treatment with MDM2 antagonist therapies
- Eligible for HSCT
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 2 - Dose Expansion KRT-232 Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b. Phase 1b - Dose Level 1 KRT-232 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. Phase 1b - Dose Level 2 KRT-232 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. Phase 1b - Dose Level 3 KRT-232 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. Phase 1b - Dose Level 4 KRT-232 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. Phase 1b - Dose Level 5 KRT-232 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. Phase 1b - Dose Level 1 TL-895 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. Phase 1b - Dose Level 2 TL-895 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. Phase 1b - Dose Level 3 TL-895 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. Phase 1b - Dose Level 4 TL-895 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. Phase 1b - Dose Level 5 TL-895 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. Phase 2 - Dose Expansion TL-895 Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b.
- Primary Outcome Measures
Name Time Method Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh) 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).
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232 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.
- Secondary Outcome Measures
Name Time Method Key Secondary Objective: To determine the overall response rate (ORR) 41 months The proportion of subjects who achieve PR or better.
Key Secondary Objective: To determine the duration of CR/CRh response (DOR) 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.
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Trial Locations
- Locations (35)
Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
🇦🇹Vienna, Austria
Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
🇺🇸Chicago, Illinois, United States
Claude Huriez Hospital
🇫🇷Lille, France
University Hospital of Nantes
🇫🇷Nantes, France
University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
🇩🇪Essen, Germany
University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
🇩🇪Hamburg, Germany
Hospital Universitario y Politécnico de La Fe
🇪🇸València, Spain
Keck School of Medicine
🇺🇸Los Angeles, California, United States
Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
University of California, Irvine Medical Center
🇺🇸Orange, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
🇺🇸Philadelphia, Pennsylvania, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
UT Southwestern Medical Center, Harold C. Simmons Cancer Center
🇺🇸Dallas, Texas, United States
University of Sunshine Coast-Sippy Downs
🇦🇺Sippy Downs, Australia
Westmead Hospital
🇦🇺Sydney, Australia
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Saint-Louis Hospital
🇫🇷Paris, France
South Lyon Hospital Center
🇫🇷Lyon, France
Paoli-Calmettes Institute
🇫🇷Marseille, France
Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
🇮🇹Meldola, Italy
University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
🇩🇪Jena, Germany
Seoul National University Hospital, Department of Hemato-Oncology
🇰🇷Seoul, Korea, Republic of
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
Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
🇩🇪Hannover, Germany
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
University Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
🇪🇸Valencia, Spain
University Hospital Germans Trias i Pujol, Department of Clinical Hematology
🇪🇸Badalona, Spain
University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
🇩🇪Halle, Sachsen-Anhalt, Germany
Hospital Center Universitaire De Nice
🇫🇷Nice, France