A Study to Investigate the Safety and Efficacy of KQB365 as Monotherapy and in Combination in Participants With Advanced Solid Malignancies

Phase 1

Recruiting

• Conditions: KRAS G12C Mutation; KRAS G12S Mutation; Solid Tumor Malignancies; CRC (Colorectal Cancer)
• Interventions: Drug: KQB365; Drug: Cetuximab

• Registration Number: NCT06720987
• Lead Sponsor: Kumquat Biosciences Inc.

Brief Summary

The goal of this clinical trial is to learn if KQB365 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB365. The main questions it aims to answer are:

* What is the safe dose of KQB365 by itself or in combination with cetuximab?

* Does KQB365 alone or in combination with cetuximab decrease the size of the tumor?

* What happens to KQB365 in the body?

Participants will:

* Receive KQB365 infusion weekly alone or in combination with cetuximab

* Visit the clinic about 9 times in the first 6 weeks, and then once every week after that.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-03
• Study First Submitted QC: 2024-12-03
• Study First Posted: 2024-12-06
• Study Start: 2025-02-04
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-30
• Primary Completion: 2029-06-30
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

Inclusion Criteria

• PART 1 (monotherapy): Histologically confirmed diagnosis of a solid tumor malignancy with either a KRAS G12C or KRAS G12S mutation.
• PART 1 (combo therapy) & PART 2: Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with either a KRAS G12C or KRAS G12S mutation.
• Unresectable or metastatic disease
• No available treatment with curative intent
• Adequate organ function
• Measurable disease per RECIST v1.1

Exclusion Criteria

• Active primary central nervous system tumors
• Cardiac abnormalities
• Active interstitial lung disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy Dose Expansion - RP2D-1	KQB365	Drug: KQB365 - Intravenous KQB365
Combo Therapy Dose Expansion - RP2D	KQB365	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab
Combo Therapy Dose Expansion - RP2D	Cetuximab	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab
Combo Therapy Dose Expansion - RP2D-1	KQB365	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab
Combo Therapy Dose Expansion - RP2D-1	Cetuximab	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab
Monotherapy Dose Expansion - RP2D	KQB365	Drug: KQB365 - Intravenous KQB365
Monotherapy Dose Escalation	KQB365	Drug: KQB365 - Intravenous KQB365
Combo Therapy Dose Escalation	KQB365	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab
Combo Therapy Dose Escalation	Cetuximab	Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab

Primary Outcome Measures

Name	Time	Method
Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1)	From enrollment to the end of treatment	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 30 days after last dose of study treatment.
Recommended Phase 2 Dose (RP2D) (Part 1)	up to 35 months	Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D.
Efficacy and Optimal Biologic Dose of study treatment, as measured by Objective Response Rate (ORR) (Part 2)	up to 35 months	ORR is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of study treatment until last dose.

Secondary Outcome Measures

Name	Time	Method
Concentration-time curve (AUC)	up to 35 months
Maximum plasma concentration (Cmax)	up to 35 months
Time to maximum plasma concentration (tmax)	up to 35 months
Overall survival (OS)	up to 35 months
Progression-free survival (PFS)	up to 35 months	using RECIST v1.1
Overall response rate (ORR)	up to 35 months	using RECIST v1.1
Duration of response (DOR)	up to 35 months	using RECIST v1.1
Time to response (TTR)	up to 35 months	using RECIST v1.1
Disease control rate (DCR)	up to 35 months	using RECIST v1.1

Trial Locations

Locations (5)

Sarah Cannon Cancer Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Cleveland Clinic, Taussig Cancer Institute; 🇺🇸 Cleveland, Ohio, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

NEXT Virginia, LLC; 🇺🇸 Fairfax, Virginia, United States