KRT-232 and TKI Study in Chronic Myeloid Leukemia

Kartos Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Chronic Myeloid Leukemia

Treatments: Drug: KRT-232; Drug: Dasatinib; Drug: Nilotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04835584

KRT-232-117

Details and patient eligibility

About

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Ph+ Chronic Myeloid Leukemia (CML) who have relapsed or are refractory or intolerant to a Tyrosine Kinase Inhibitor (TKI).

This study is a global, open label Phase 1b/2 to determine the efficacy and safety of KRT-232 in patients with chronic phase CML (CML-CP) and accelerated phase (CML-AP) who have failed TKI treatments.

Enrollment: 109 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Phase 1b and Phase 2 Arms A and B: Documented TP53wt, Ph+, BCR-ABL+ CML-CP
• Phase 2 Arm C ONLY: Documented TP53wt, Ph+, BCR-ABL+ CML-AP
• Subject is resistant (relapsed or refractory) and/or intolerant to at least 1 prior TKI.
• Adults ≥ 18 years of age.
• ECOG performance status of 0 to 2
• Adequate hematologic, hepatic, and renal functions

Exclusion criteria

• Phase 1b and Phase 2 Arms A and B: Documented Ph+, BCR-ABL+ CML-AP
• Documented Ph+, BCR-ABL+ CML-BC
• Known T315I mutation.
• Prior treatment with MDM2 antagonist therapies.
• Intolerance to current TKI therapy.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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109 participants in 4 patient groups

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP

Experimental group

Description:

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule.

Treatment:

Drug: Nilotinib

Drug: KRT-232

Drug: Dasatinib

Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP)

Experimental group

Description:

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasastinib will be administered orally, per locally prescribed dose and schedule.

Treatment:

Drug: KRT-232

Drug: Dasatinib

Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP)

Experimental group

Description:

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Nilotinib will be administered orally, per locally prescribed dose and schedule.

Treatment:

Drug: Nilotinib

Drug: KRT-232

Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

Experimental group

Description:

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule.

Treatment:

Drug: Nilotinib

Drug: KRT-232

Drug: Dasatinib