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

Telios Pharma

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: TL-895; Drug: KRT-232

Study type: Interventional

Funder types: Industry

Identifiers

NCT04669067

TL-895-203

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 6 patient groups

Phase 1b - Dose Level 1

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: KRT-232

Phase 1b - Dose Level 2

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: KRT-232

Phase 1b - Dose Level 3

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: KRT-232

Phase 1b - Dose Level 4

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: KRT-232

Phase 1b - Dose Level 5

Experimental group

Description:

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.

Treatment:

Drug: TL-895

Drug: KRT-232

Phase 2 - Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: TL-895

Drug: KRT-232