This phase I trial tests the safety, side effects, and best dose of pidnarulex (CX-5461) in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic). Pidnarulex is an oral inhibitor of ribonucleic acid polymerase I, with potential antineoplastic activity. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill cancer cells.
Patients must have histologically confirmed solid tumors with metastatic disease that have progressed after ≥ 1 line of prior therapy and/or for whom no standard treatment is available that has been shown to improve survival.
Patients must have a molecular testing report to assess HRD mutation status prior to enrollment.
Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam).
Patients must have a tumor site amenable to biopsy.
Patients must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia).
Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of pidnarulex will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. A list of agents that interact with CYP450 isoenzymes is provided. For medications or substances not listed, or in cases of uncertainty, the principal investigator may consult with a medical expert or a pharmacologist to make an informed decision regarding eligibility.
History of allergic reactions attributed to inactive ingredients in the drug product.
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
Single group
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Pidnarulex
Biological/VaccineGiven IV
RAD51 response
Will be defined as at least 5 percent of cells with at least 5 positive foci per nucleus. Will target a 30% Rad51 response rate. Will be compared descriptively across the 2 cohorts, with and without homologous repair deficiency mutations.
Incidence of adverse events
Will be summarized using Common Terminology Criteria for Adverse Events version 5.0.
Overall response
Pharmacokinetics (PK)
PK will be measured using plasma.
Deoxyribonucleic acid (DNA) damage and repair signaling markers
Genomic alterations
Will be measured using circulating tumor DNA. Will be assessed using non-parametric analyses.
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