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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04669067
Recruitment Status : Recruiting
First Posted : December 16, 2020
Last Update Posted : October 12, 2022
Sponsor:
Collaborator:
Kartos Therapeutics, Inc.
Information provided by (Responsible Party):
Telios Pharma, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: TL-895 Drug: KRT-232 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 31, 2021
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2025


Arm Intervention/treatment
Experimental: Phase 1b - Dose Level 1
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.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

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

Experimental: Phase 1b - Dose Level 2
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.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

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

Experimental: Phase 1b - Dose Level 3

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.

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

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

Experimental: Phase 1b - Dose Level 4

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.

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

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

Experimental: Phase 1b - Dose Level 5

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.

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

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

Experimental: Phase 2 - Dose Expansion
Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b.
Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

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




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh) [ Time Frame: 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 Outcome Measures :
  1. Key Secondary Objective: To determine the overall response rate (ORR) [ Time Frame: 41 months ]
    The proportion of subjects who achieve PR or better.

  2. Key Secondary Objective: To determine the duration of CR/CRh response (DOR) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04669067


Contacts
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Contact: John Mei 650-542-0136 jmei@teliospharma.com
Contact: Evelyn Hang 650-980-7779 ehang@teliospharma.com

Locations
Show Show 36 study locations
Sponsors and Collaborators
Telios Pharma, Inc.
Kartos Therapeutics, Inc.
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Responsible Party: Telios Pharma, Inc.
ClinicalTrials.gov Identifier: NCT04669067    
Other Study ID Numbers: TL-895-203
First Posted: December 16, 2020    Key Record Dates
Last Update Posted: October 12, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Telios Pharma, Inc.:
AML
TP53
FLT3+
Navtemadlin
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms