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

PRIMARY OBJECTIVE: I. To assess whether pidnarulex induces a Rad51 response, which will be determined by an integral biomarker of percentage of cells with Rad51 nuclear foci in tumor biopsy specimens in patients with and without homologous repair deficiency (HRD) genetic mutations. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of pidnarulex. II. To determine the overall response rate (complete responses plus partial responses) in patients with advanced, refractory solid tumors. III. To measure the pharmacokinetics of pidnarulex. IV. To evaluate other DNA damage and repair signaling markers including Top2, G4 stabilization, RPA32, pSer33-RPA32, γH2AX, 53BP1, pSer8-RPA32, pKap1m and pNBS1. EXPLORATORY OBJECTIVE: I. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance. OUTLINE: Patients receive pidnarulex intravenously (IV) over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI), biopsy, and collection of blood samples throughout the trial. Patients may undergo echocardiography (ECHO) at screening and then as clinically indicated. After completion of study treatment, patients are followed up at 30 days.