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

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)

Status

UNKNOWN

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04669067

Enrollment

Registered

2020-12-16

Start date

2021-03-31

Completion date

2025-11-30

Last updated

2023-02-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukemia

Keywords

AML, TP53, FLT3+, Navtemadlin

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.

Interventions

DRUGTL-895

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

DRUGKRT-232

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
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.
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).

Secondary

Measure	Time frame	Description
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.

Countries

Australia, Austria, France, Germany, Italy, South Korea, Spain, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026