Adult, Hematologic Malignancies
Conditions
Keywords
CML, dasatinib
Brief summary
The goal of this clinical trial is to learn if KQB198 works to treat advanced hematologic malignancies in adults. It will also learn about the safety of KQB198. The main questions it aims to answer are: * What is the safe dose of KQB198 by itself or in combination with other anti-cancer drugs? * Does KQB198 alone or in combination with other anti-cancer drugs decrease the size of the tumor? * What happens to KQB198 in the body? Participants will: * Take KQB198 daily, alone or in combination with another anti-cancer drug * Visit the clinic about 8 times in the first 8 weeks, and then once every 4 weeks after that
Interventions
DRUGKQB198
Oral KQB198
DRUGDasatinib
Oral dasatinib
Sponsors
Kumquat Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adequate organ function Part 1 and Part 2, Cohort B Participants Only: • Ph+ CML in chronic phase who have been previously treated with at least 2 different tyrosine kinase inhibitors (TKIs) and are relapsed from or intolerant to those TKIs and ineligible for alternative therapeutic options likely to produce clinical benefit as determined by the investigator. Part 2, Cohort A Participants Only: • Participants with Ph+ CML in chronic phase who are on dasatinib prior to study entry and have a warning or failure to dasatinib as determined by the investigator per ELN 2020 guidelines
Exclusion criteria
* CML in accelerated or blast phase * Prior therapy with a similar mechanism of action to KQB198 * History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow * History of interstitial lung disease * Cardiac abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1) | 28 Days | Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, SAEs, and DLTs, from first dose of study treatment to 28 days after last dose of study treatment. |
| Recommended Phase 2 Dose (RP2D) (Part 1) | Up to 30 months | Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D. |
| Efficacy of study treatment and optimal biologic dose, as measured by molecular response (MR) per European Leukemia Network (ELN) 2020 Guidelines (Part 2). | Up to 6 Months | Molecular response is the percentage of BCR-ABL fusion protein found in blood. Calculation of molecular response in Part 2 Cohort A will be the proportion of subjects that experience molecular response 4 (MR4) during the time period from 1st dose of study treatment until 6 months of study treatment. Calculation of molecular response in part 2 cohort B will be the proportion of subjects that experience molecular response 3 (MR3) during the time period from 1st dose of study treatment until 6 months of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Study Treatment | Up to 30 months | Efficacy of study treatment as measured by molecular response (MR) at 3, 6, 9, and 12 months, and anytime. |
| Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 2) | 28 Days After Last Dose | Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, SAEs from first dose of study treatment to 28 days after last dose of study treatment. |
| Concentration-Time Curve (AUC) | Up to 30 months | — |
| Maximum Plasma Concentration (Cmax) | Up to 30 months | — |
| Time to Maximum Plasma Concentration (tmax) | Up to 30 months | — |
Countries
France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Outcome results
None listed