This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, pharmacokinetics (PK), and biomarker study of CBX-12 in subjects with advanced or metastatic refractory solid tumors.
Phase 1 is the dose-escalation portion of the study in which the safety and tolerability of three dosing schedules of CBX-12 will be evaluated. Subjects in Part A will be treated with CBX-12 on a daily x 5 every 3 weeks schedule (treatment in Part A was discontinued in October 2021). Subjects in Phase 1 Part B will be treated with CBX-12 on a daily x 3 every 3 weeks schedule. Subjects in Phase 1 Part C will be treated with CBX-12 once weekly. Subjects in Phase 1 Modified Part B will be treated with CBX-12 once every 3 weeks. For all parts in Phase 1, after all subjects in a cohort have completed treatment through the DLT period or discontinued treatment due to a DLT, the SRC, composed of the Investigators who have enrolled subjects in the current cohort(s), the study Medical Monitor and ad hoc members (e.g., other Investigators, a statistician) as needed, will review all available safety data, including DLTs and all available PK data for that cohort and make dose-level recommendations. Once the recommended phase 2 dose (RP2D) has been established in Part B, Part C and Modified Part B, Phase 2 expansion cohorts may open.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
130
CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety
Yale Cancer Center
New Haven, Connecticut, United States
NEXT Oncology
Austin, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
NCI CTCAE v5.0
Time frame: Through the end of study, estimated as 6 months
Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B)
Safety Review Committee Analysis of Safety and PK Data
Time frame: 15 months
Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)
Safety Review Committee Analysis of Safety and PK Data
Time frame: 15 months
Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B)
Safety Review Committee Analysis of Safety and PK Data
Time frame: 15 months
Phase 2: Overall response rate (ORR)
ORR Based on RECIST v1.1
Time frame: Through the end of study, estimated as 6 months
Maximum concentration of CBX-12
PK Analysis
Time frame: 5 days
Area under the curve from 0-24 hours of CBX-12
PK Analysis
Time frame: 5 days
Time to maximum concentration of CBX-12
PK Analysis
Time frame: 5 days
Half-life of CBX-12
PK Analysis
Time frame: 5 days
Clearance (CL) of CBX-12
PK Analysis
Time frame: 5 days
Apparent Volume of Distribution at Steady State (Vss) CBX-12
PK Analysis
Time frame: 5 days
Phase 1: ORR
Based on RECIST v1.1
Time frame: Through the end of study, estimated as 6 months
Duration of Response (DoR)
Based on RECIST v1.1
Time frame: Through the end of study, estimated as 6 months
Progression-free Survival (PFS)
Based on RECIST v1.1
Time frame: Through the end of study, estimated as 6 months
Phase 2: Incidence of TEAEs
NCI CTCAE v5.0
Time frame: Through the end of study, estimated as 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.