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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| TL-895 | | TL-895 combined with KRT-232 |
| KRT-232 | | TL-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
| Name | Type | Description | Interventions |
|---|
| TL-895 combined with KRT-232 | Experimental | TL-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. | |
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
Last Updated
August 5, 2021
