A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Optimization Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of KQB365 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies With KRAS G12S or G12C Mutations
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, in combination with cetuximab, or in combination with KQB198? * Does KQB365 alone, in combination with cetuximab, or in combination with KQB198 decrease the size of the tumor? * What happens to KQB365 in the body? Participants will: * Receive KQB365 infusion weekly alone, in combination with cetuximab, or in combination with oral KQB198. * Visit the clinic about 9 times in the first 6 weeks, and then once every week after that.
Arms & interventions
- DrugKQB365
Intravenous KQB365
- DrugCetuximab
Intravenous cetuximab
- DrugKQB198
Oral KQB198
Outcome measures
Primary
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 30 days after last dose of study treatment.
Time frame: From enrollment to the end of treatment
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 35 months
Efficacy and Optimal Biologic Dose of study treatment, as measured by Objective Response Rate (ORR) (Part 2)
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.
Time frame: up to 35 months
Secondary
Concentration-time curve (AUC)
Time frame: up to 35 months
Maximum plasma concentration (Cmax)
Time frame: up to 35 months
Time to maximum plasma concentration (tmax)
Time frame: up to 35 months
Overall survival (OS)
Time frame: up to 35 months
Progression-free survival (PFS)
Time frame: up to 35 months
Overall response rate (ORR)
Time frame: up to 35 months
Duration of response (DOR)
Time frame: up to 35 months
Time to response (TTR)
Time frame: up to 35 months
Disease control rate (DCR)
Time frame: up to 35 months
Eligibility criteria
Study locations (11)
Mayo Clinic, Phoenix
Phoenix, Arizona, 85054
Sarah Cannon Cancer Institute at HealthONE
Denver, Colorado, 80218
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
START Midwest
Grand Rapids, Michigan, 49546
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
Cleveland Clinic, Taussig Cancer Institute
Cleveland, Ohio, 44195
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Sydney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
NEXT Oncology
San Antonio, Texas, 78229
NEXT Virginia, LLC
Fairfax, Virginia, 22031