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

A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of KQB198 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hematologic Malignancies

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 Overview

• Status: Active, not recruiting
• Conditions: Hematologic Malignancies; Adult
• Intervention / Treatment: Drug: KQB198; Drug: Dasatinib

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13005
    • AP-HM - Hôpital de la Timone
  • Centre-Val de Loire
    • Tours, Centre-Val de Loire, France, 37044
      • CHRU de Tours - Hôpital Bretonneau
• Germany
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover (MHH)
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Universitaetsklinikum Jena
• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
  • Lombardy
    • Milan, Lombardy, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda
  • Milan, Lombardy
    • Milan, Milan, Lombardy, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Stichting Radboud Universitair Medisch Centrum
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-185
      • AIDPORT Sp. z o.o.
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-519
      • Pratia Onkologia Katowice
• Spain
  • Andalusia
    • Málaga, Andalusia, Spain, 29010
      • Hospital Regional Universitario de Málaga
  • Catalonia
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08908
      • Institut Catala d'Oncologia - L'Hospitalet
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid, Spain, 28046
      • Hospital Universitario La Paz
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, W12 0HS
      • Hammersmith Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco (UCSF)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Cincinnati
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) - Transplant and Cellular Therapy Operations
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Austin Central
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation	Drug: KQB198; Oral KQB198
Experimental: Combo Therapy Dose Escalation	Drug: KQB198; Oral KQB198; Drug: Dasatinib; Oral dasatinib
Experimental: Combo Therapy Dose Expansion - RP2D	Drug: KQB198; Oral KQB198; Drug: Dasatinib; Oral dasatinib
Experimental: Combo Therapy Dose Expansion - RP2D-1	Drug: KQB198; Oral KQB198; Drug: Dasatinib; Oral dasatinib
Experimental: Monotherapy Dose Expansion - RP2D	Drug: KQB198; Oral KQB198
Experimental: Monotherapy Dose Expansion - RP2D -1	Drug: KQB198; Oral KQB198

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Kumquat Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CML; dasatinib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Pyrimidines; Dasatinib
• Other Study ID Numbers: KQB198-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No