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

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.