A Study to Investigate the Safety and Efficacy of KQB198 as Monotherapy and in Combination in Participants With Advanced Hematologic Malignancies

Phase 1Active Not RecruitingNCT06645886

Kumquat Biosciences Inc.13 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematologic Malignancies Adult

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (29)

University of California, San Francisco (UCSF)

San Francisco, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Duke University Medical Center

Durham, North Carolina, United States

Outcomes

Primary Outcomes

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.

Time frame: 28 Days

Recommended Phase 2 Dose (RP2D) (Part 1)

Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D.

Time frame: 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.

Time frame: Up to 6 Months

Secondary Outcomes

Efficacy of Study Treatment

Efficacy of study treatment as measured by molecular response (MR) at 3, 6, 9, and 12 months, and anytime.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 28 Days After Last Dose

Concentration-Time Curve (AUC)

Time frame: Up to 30 months

Maximum Plasma Concentration (Cmax)

Time frame: Up to 30 months

Time to Maximum Plasma Concentration (tmax)

Time frame: Up to 30 months