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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:
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Monotherapy Dose Escalation | Experimental |
| |
| Combo Therapy Dose Escalation | Experimental |
| |
| Combo Therapy Dose Expansion - RP2D | Experimental |
| |
| Combo Therapy Dose Expansion - RP2D-1 | Experimental |
| |
| Monotherapy Dose Expansion - RP2D | Experimental |
| |
| Monotherapy Dose Expansion - RP2D -1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KQB198 | Drug | Oral KQB198 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1) | 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. | 28 Days |
| Recommended Phase 2 Dose (RP2D) (Part 1) | Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D. | Up to 30 months |
| Efficacy of study treatment and optimal biologic dose, as measured by molecular response (MR) per European Leukemia Network (ELN) 2020 Guidelines (Part 2). | 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. | Up to 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Study Treatment | Efficacy of study treatment as measured by molecular response (MR) at 3, 6, 9, and 12 months, and anytime. | Up to 30 months |
| Efficacy of Study Treatment | Efficacy of study treatment as measured by duration of response (DOR). DOR is defined as the time from the date when the response is first observed till the date the response is lost or death, whichever is earlier. |
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Inclusion Criteria:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco (UCSF) | San Francisco | California | 94143 | United States | ||
| Colorado Blood Cancer Institute |
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| Dasatinib | Drug | Oral dasatinib |
|
| Up to 30 Months |
| Efficacy of Study Treatment | Efficacy of study treatment as measured by time to response (TTR). Response assessments will be summarized by all reported response categories at each visit. | Up to 30 months |
| Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 2) | 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. | 28 Days After Last Dose |
| 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 |
| Denver |
| Colorado |
| 80218 |
| United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Oncology Hematology Cincinnati | Cincinnati | Ohio | 45236 | United States |
| Sarah Cannon Research Institute (SCRI) - Transplant and Cellular Therapy Operations | Nashville | Tennessee | 37203 | United States |
| Texas Oncology Austin Central | Austin | Texas | 78731 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Virginia Cancer Specialists | Fairfax | Virginia | 22031 | United States |
| CHRU de Tours - Hopital Bretonneau | Tours | Centre-Val de Loire | 37044 | France |
| AP-HM - Hopital de la Timone | Marseille | 13005 | France |
| Medizinische Hochschule Hannover (MHH) | Hanover | Lower Saxony | 30625 | Germany |
| Universitaetsklinikum Jena | Jena | Thuringia | 07747 | Germany |
| IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola | Bologna | Bologna | 40138 | Italy |
| Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore | Rome | Lazio | 00168 | Italy |
| ASST Grande Ospedale Metropolitano Niguarda | Milan | Lombardy | 20162 | Italy |
| Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano | Milan | Milan, Lombardy | 20122 | Italy |
| Stichting Radboud Universitair Medisch Centrum | Nijmegen | Gelderland | 6525 | Netherlands |
| Aidport Sp. z o.o. | Poznan | Greater Poland Voivodeship | 60-185 | Poland |
| Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii | Gdansk | Pomeranian Voivodeship | 80-214 | Poland |
| Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii | Gdansk | Pomeranian Voivodeship | 80-952 | Poland |
| Pratia Onkologia Katowice | Katowice | Silesian Voivodeship | 40-519 | Poland |
| Hospital Regional Universitario de Malaga | Málaga | Andalusia | 29010 | Spain |
| Institut Catala d'Oncologia - L'Hospitalet | L'Hospitalet de Llobregat | Catalonia | 08908 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | Madrid | 28041 | Spain |
| Hospital Universitario La Paz | Madrid | Madrid | 28046 | Spain |
| Hammersmith Hospital | London | Greater London | W12 0HS | United Kingdom |
| Nottingham University Hospitals | Nottingham | Nottinghamshire | NG5 1PB | United Kingdom |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
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