A Study to Investigate the Safety and Efficacy of KQB548 in Participants With Advanced Solid Malignancies

A Phase 1a, Open-label, Multicenter, Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of KQB548 in Participants With Advanced Solid Malignancies With a KRAS G12D Mutation

The goal of this trial is to learn if KQB548 works to treat patients with advanced solid malignancies with a KRAS G12D mutation. It will also learn about the safety of KQB548. The main questions it aims to answer are:

• What is the safe dose of KQB548?
• Does KQB548 decrease the size of the tumor?
• What happens to KQB548 in the body?

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor Malignancies
• Intervention / Treatment: Drug: KQB548

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kumquat Clinical Development; Phone Number: 858-214-2700; Email: kumquatstudies@kumquatbio.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California, San Diego
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • SCRI - Denver
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami - Sylvester Comprehensive Cancer Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology - Austin
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • Irving, Texas, United States, 75039
      • Recruiting
      • Next Oncology - Dallas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology - San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah - Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • Fred Hutchison Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed, locally advanced or metastatic PDAC, CRC, or NSCLC with a KRAS G12D mutation
• Progressed on, or intolerant to at least one prior line of systemic standard of care therapy
• Measurable disease according to RECIST v1.1
• Adequate organ function

Exclusion Criteria:

• Previous treatment with a KRAS G12D inhibitor or pan-RAS inhibitor
• History of intestinal disease, uncontrolled inflammatory bowel disease (e.g., Crohn's disease, Ulcerative Colitis), major esophageal or gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study intervention or result in inability to swallow oral medications
• Poorly controlled ascites and/or pleural effusion
• Requires treatment with a strong and/or moderate CYP3A inhibitor or inducer
• Requires treatment with a proton-pump inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation	Drug: KQB548; Oral KQB548

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety,Tolerability, MTD/MAD and/or RDE in the Study Population	Safety characterized by type, incidence and severity of treatment emergent adverse events (TEAEs), SAEs, and DLTs	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma 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
Overall Response Rate (ORR)	Per RECIST v1.1	Up to 30 months
Duration of Response (DOR)	Per RECIST v1.1	Up to 30 months
Time to Response (TTR)	Per RECIST v1.1	Up to 30 months
Disease Control Rate (DCR)	Per RECIST v1.1	Up to 30 months
Progression Free Survival (PFS)	Per RECIST 1.1	Up to 30 months
Overall Survival (OS)	Per RECIST v1.1	Up to 30 months
Peak Plasma Concentration (Cmax) in Fed and Fasted States for Food Effect		Up to 30 months
Concentration Time Curve (AUC) in Fed and Fasted States for Food Effect		Up to 30 months
Time to maximum plasma concentration (tmax) in Fed and Fasted States for Food Effect		Up to 30 months
Evaluate Changes in QTc (mSec)		Up to 30 months

Collaborators and Investigators

• Sponsor: Kumquat Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: September 3, 2025
• First Submitted That Met QC Criteria: October 2, 2025
• First Posted (Actual): October 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: KRAS; G12D
• Other Study ID Numbers: KQB548-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No