NCT05691517

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers

Pilot Study of CBX-12 Pharmacodynamics in Patients With Advanced Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). CBX-12 works by binding to a protein called TOP1 that is present inside the cells. This allows CBX-12 to kill the cancer cells by damaging their DNA, resulting in cancer cell death. This trial is being done to find out if this approach is better or worse than the usual approach for advanced cancers.

Detailed description

PRIMARY OBJECTIVE: I. Assess the effects of CBX-12 on biomarkers of DDR in biopsy specimens from patients with advanced solid tumors at baseline and 24-30 hours post-first dose to establish the degree and duration of CBX-12 target engagement. SECONDARY OBJECTIVES: I. Assess the effects of CBX-12 on tumor TOP1 molecular response at baseline and 24-30 hours post-first dose. II. Determine any association between tumor TOP1 and DDR modulation and plasma exatecan concentrations. III. Evaluate the effects of CBX-12 on CD8 T cell infiltration and activation in tumor. IV. Determine the objective response rate (ORR) of patients with advanced cancers to CBX-12 using RECIST v 1.1. V. Assess safety and tolerability of CBX-12. EXPLORATORY OBJECTIVES: I. Measure the effects of CBX-12 on molecular markers of apoptosis. II. Examine any genomic or gene expression characteristics in tumor that may be associated with sensitivity or resistance to CBX-12. III. Examine any genomic alterations in circulating free deoxyribonucleic acid (DNA) (cfDNA) that may be associated with sensitivity or resistance to CBX-12. IV. Measure changes in levels of any anti-drug antibodies that may develop during CBX-12 therapy (Cybrexa assay). V. Examine the molecular context of drug sensitivity or resistance (e.g., SLFN11 expression). OUTLINE: Patients receive CBX-12 intravenously (IV), over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and computed tomography (CT) scans on study and undergo blood sample collection throughout the trial. After completion of study treatment, patients follow up at 30 days.

Conditions

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	pH Low Insertion Peptide-exatecan Conjugate CBX-12	Given IV

Timeline

• Start date: 2024-06-12
• Primary completion: 2026-10-15
• Completion: 2026-10-15
• First posted: 2023-01-20
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study