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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04669067




Registration number
NCT04669067
Ethics application status
Date submitted
2/12/2020
Date registered
16/12/2020
Date last updated
17/02/2023

Titles & IDs
Public title
TL-895 and KRT-232 Study in Acute Myeloid Leukemia
Scientific 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)
Secondary ID [1] 0 0
TL-895-203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TL-895
Treatment: Drugs - KRT-232

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.

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.

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.

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.

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.

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.


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

Treatment: Drugs: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
Timepoint [1] 0 0
13 months
Primary outcome [2] 0 0
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
Timepoint [2] 0 0
41 months
Secondary outcome [1] 0 0
Key Secondary Objective: To determine the overall response rate (ORR)
Timepoint [1] 0 0
41 months
Secondary outcome [2] 0 0
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Timepoint [2] 0 0
41 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- AML subtype 3

- Prior treatment with MDM2 antagonist therapies

- Eligible for HSCT

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2025
Actual
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Sunshine Coast-Sippy Downs - Sippy Downs
Recruitment hospital [2] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Austria
State/province [10] 0 0
Linz
Country [11] 0 0
Austria
State/province [11] 0 0
Vienna
Country [12] 0 0
France
State/province [12] 0 0
Lille
Country [13] 0 0
France
State/province [13] 0 0
Lyon
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Nantes
Country [16] 0 0
France
State/province [16] 0 0
Nice
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Sachsen-Anhalt
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Hamburg
Country [21] 0 0
Germany
State/province [21] 0 0
Hannover
Country [22] 0 0
Germany
State/province [22] 0 0
Jena
Country [23] 0 0
Italy
State/province [23] 0 0
Ancona
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Meldola
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Incheon
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Spain
State/province [28] 0 0
Badalona
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Valencia
Country [31] 0 0
Spain
State/province [31] 0 0
València

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Telios Pharma, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Kartos Therapeutics, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04669067
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04669067