Study of CBX-12 in Subjects with Advanced or Metastatic Refractory Solid Tumors
- Conditions
- Epithelial Ovarian CancerPancreas CancerNon-small Cell Lung CancerUrothelial CarcinomaSolid Tumor, AdultSmall Cell Lung CarcinomaAppendix CancerSarcomaBreast CancerColorectal Cancer
- Interventions
- Registration Number
- NCT04902872
- Lead Sponsor
- Cybrexa Therapeutics
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 130
- Subject has a histologically- or cytologically-diagnosed solid tumor which is advanced or metastatic and which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists. Subject's prior treatment should include all approved regimens that have demonstrated a survival advantage for the subject's disease, stage, and line of therapy.
- Has measurable disease per RECIST 1.1.
- An adequate tumor sample must be available from core needle biopsies obtained during the Screening Period and following the subject's most recent systemic therapy.
- Agrees to an on-treatment biopsy preferably of the same lesion from which the pre-CBX-12 treatment sample was obtained as long as the Investigator determines such biopsy can be performed with acceptable safety. (Removed Amd 4, date 31-Mar-2023)
- Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy less than or equal to 3 weeks prior to the first dose of CBX-12. The interval may be reduced to 2 weeks for bone only radiation therapy or investigational agents not expected to be associated with adverse events (AEs) after 2 weeks of last administration, with Medical Monitor approval.
- Small-molecule kinase inhibitors or hormonal agents less than or equal to 14 days prior to the first dose of CBX-12.
- Subjects who are currently receiving any other anti cancer or investigational agent(s).
- Clinically significant intercurrent disease.
- Subjects with primary central nervous system (CNS) tumors or clinically active CNS metastases or carcinomatous meningitis. Subjects with stable brain metastasis may be enrolled with Medical Monitor approval.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 Schedule A Dose Escalation (Daily Dosing x 5) CBX-12 CBX-12 administered on a daily x 5, 3 week schedule Phase 2 Metastatic Breast Expansion Cohort CBX-12 CBX-12 administered TBD Phase 1 Schedule B Dose Escalation (Daily Dosing x 3) CBX-12 CBX-12 administered on a daily x 3, 3 week schedule Phase 1 Schedule C Dose Escalation (Once Weekly Dosing ) CBX-12 CBX-12 administered once weekly, 4 week schedule Phase 2 Ovarian Cancer Expansion Cohort CBX-12 CBX-12 administered TBD Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks) CBX-12 CBX-12 administered once every 3 weeks
- Primary Outcome Measures
Name Time Method Phase 1: Incidence of treatment-emergent adverse events (TEAEs) Through the end of study, estimated as 6 months NCI CTCAE v5.0
Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B) 15 months Safety Review Committee Analysis of Safety and PK Data
Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B) 15 months Safety Review Committee Analysis of Safety and PK Data
Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C) 15 months Safety Review Committee Analysis of Safety and PK Data
Phase 2: Overall response rate (ORR) Through the end of study, estimated as 6 months ORR Based on RECIST v1.1
- Secondary Outcome Measures
Name Time Method Maximum concentration of CBX-12 5 days PK Analysis
Area under the curve from 0-24 hours of CBX-12 5 days PK Analysis
Time to maximum concentration of CBX-12 5 days PK Analysis
Half-life of CBX-12 5 days PK Analysis
Clearance (CL) of CBX-12 5 days PK Analysis
Progression-free Survival (PFS) Through the end of study, estimated as 6 months Based on RECIST v1.1
Apparent Volume of Distribution at Steady State (Vss) CBX-12 5 days PK Analysis
Phase 1: ORR Through the end of study, estimated as 6 months Based on RECIST v1.1
Duration of Response (DoR) Through the end of study, estimated as 6 months Based on RECIST v1.1
Phase 2: Incidence of TEAEs Through the end of study, estimated as 6 months NCI CTCAE v5.0
Trial Locations
- Locations (3)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States