Testing How the Body Responds to the Drug CX-5461 (Pidnarulex) in Patients With Metastatic Solid Cancers

Recruiting now · Phase 1

Conditions studied: Metastatic Malignant Solid Neoplasm

In brief

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.

Key facts

Study ID

NCT06606990

Run by

National Cancer Institute (NCI)

People needed

40

Starts

2025-07-01

Expected to finish

2026-12-31

Last updated by the study team

2026-05-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Age ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥ 70%).
• Absolute neutrophil count ≥ 1,500/mcL.
• Hemoglobin ≥ 9 g/dL.
• Platelets ≥ 100,000/mcL.
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• (However, patients with known Gilbert disease who have serum bilirubin level of up to 3 mg/dl may be enrolled).
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 institutional upper limit of normal (ULN).
• Subjects may receive supplementation to meet this eligibility criteria.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN.
• (AST and/or ALT ≤ 5 x ULN for patients with liver involvement).
• Potassium ≥ lower limit of normal (LLN).
• Subjects may receive supplementation to meet this eligibility criteria.
• Magnesium ≥ LLN.
• Subjects may receive supplementation to meet this eligibility criteria.
• Ionized or corrected calcium ≥ LLN.
• Subjects may receive supplementation to meet this eligibility criteria.
• Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance levels ≥ 60 ml/min based on the Cockcroft-Gault formula.
• Oxygen (O2) saturation > 90% on room air.
• Prior standard or investigational therapy must have been completed ≥ 4 weeks or ≥ 5 half-lives of the prior agent (whichever is shorter) prior to enrollment; the exception is ≥ 2 weeks since any investigational agent administered (at a sub-therapeutic dose) as part of a phase 0 study.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

You may not qualify if…

• 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.
• Pregnant and lactating women are excluded from this trial. The exclusion is based on the potential risk of adverse effects of pidnarulex on fetal development and newborn health. The safety of pidnarulex has not been established in pregnant or lactating women, and there is a possibility that the drug could cause harm to the developing fetus or be transferred to the infant through breast milk. Additionally, the physiological changes that occur during pregnancy and lactation could alter the pharmacokinetics and pharmacodynamics of pidnarulex, leading to unpredictable drug exposure and efficacy.
• Patients with chronic, active HBV or HCV infections that require ongoing antiviral treatment will be excluded from the trial. This exclusion is due to the potential for drug interactions with the study medication and the risk of exacerbating liver disease.
• Patients with cirrhosis, regardless of the etiology, will be excluded from participation in the trial. This is due to the increased risk of complications and adverse events associated with the study medication in this population.
• Presence of known photosensitivity disorders (xeroderma pigmentosa, porphyria etc.). Patients who do not agree to use sunglasses and sun blocker (with sun protection factor 50 [SPF50] to ultraviolet B [UVB] and a high degree of protection against ultraviolet A [UVA]) if exposed to sunlight during the course of the study and for 3 months after the last dose are not eligible. Appropriate sunscreen products will be provided. Patients who plan to use sun beds or tanning booths during the course of the study and within 3 months after the last dose are not eligible.
• Active ocular surface disease at baseline (based on ophthalmological evaluation).
• History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).

Where it is running

• National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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