Clinical Trials /

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

NCT04669067

Description:

This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with 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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: TL-895-203
  • NCT ID: NCT04669067

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
TL-895TL-895 combined with KRT-232
KRT-232TL-895 combined with KRT-232

Purpose

This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with 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.

Trial Arms

NameTypeDescriptionInterventions
TL-895 combined with KRT-232ExperimentalTL-895 will be administered orally, twice a day (BID) continuously starting on Day 1 in a 28-day cycle. KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
  • TL-895
  • KRT-232

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
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.

Secondary Outcome Measures

Measure:Key Secondary Objective: To characterize the peak plasma concentration (Cmax) of TL-895 and KRT-232
Time Frame:13 months
Safety Issue:
Description:Cmax of TL-895 and KRT-232
Measure:Key Secondary Objective: To characterize the area under the plasma concentration versus time curve (AUC) of TL-895 and KRT-232
Time Frame:13 months
Safety Issue:
Description:AUC of TL-895 and KRT-232
Measure:Key Secondary Objective: To characterize the time to Cmax (Tmax) of TL-895 and KRT-232
Time Frame:13 months
Safety Issue:
Description:Tmax of TL-895 and KRT-232
Measure:Key Secondary Objective: To determine the overall response rate (ORR)
Time Frame:41 months
Safety Issue:
Description:The proportion of subjects who achieve PR or better.
Measure:Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Time Frame:41 months
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Telios Pharma, Inc.

Trial Keywords

  • AML
  • TP53
  • FLT3+

Last Updated

May 12, 2021