Investigational Drug
CX-5461
TrialFetch AI Analysis
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Overview
CX-5461 (pidnarulex) is an investigational anticancer drug studied mainly in early-phase trials involving advanced cancers. Human trial results are available, but they do not yet establish whether it improves survival or other long-term outcomes. (nature.com)
Mechanism of action
CX-5461 was developed to inhibit RNA polymerase I–mediated ribosomal RNA production. Research also identifies it as a stabilizer of DNA G-quadruplexes—structures that can interfere with DNA replication and repair. This may make tumors with homologous-recombination repair defects, including some with BRCA1/2 or PALB2 alterations, particularly susceptible. Its mechanisms are still being investigated. (pubmed.ncbi.nlm.nih.gov)
Efficacy
- In a published phase I solid-tumor trial involving 40 treated patients, researchers reported responses in 14%, primarily among patients with defective homologous recombination. (nature.com)
- In a separate phase I hematologic-cancer trial, one of 16 patients had a prolonged partial response; five had stable disease as their best response. (sciencedirect.com)
- A 2026 conference abstract from a phase Ib solid-tumor study reported partial responses in 1 of 29 response-evaluable patients in its main cohort and 2 of 29 response-evaluable patients with ovarian cancer. These cohorts overlap, so the figures should not be added together. The findings remain preliminary. (ascopubs.org)
Safety
Light-related skin toxicity has been a prominent adverse effect. In the published solid-tumor trial, treatment-related grade 3–4 events included skin phototoxicity (15%), hand–foot syndrome (2.5%), and nausea (2.5%). In the 2026 phase Ib abstract, 12 of 54 patients (22%) had grade 3 or higher treatment-related adverse events, including proteinuria, low platelet counts, and fatigue. (nature.com)
Further reading
- Published phase I solid-tumor trial
- Published phase I hematologic-cancer trial
- 2026 phase Ib trial abstract
Last updated: Sep 2026
Active trials using CX-5461
Found 3 active trials using this drug:
TrialFetch AI summary: Adults with refractory, unresectable or metastatic microsatellite-stable colorectal cancer receive investigational pidnarulex, an RNA polymerase I inhibitor that may also stabilize DNA G-quadruplexes, alone or with cemiplimab, an anti-PD-1 antibody. The randomized portion requires liver metastases and MYC amplification or a deleterious FBXW7 mutation.
ClinicalTrials.gov ID: NCT07147231
TrialFetch AI summary: Adults with previously treated, advanced HER2-expressing solid tumors are eligible for dose escalation; expansion is limited to HER2-low breast cancer or hormone receptor–positive HER2-ultralow breast cancer. Patients receive trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate, plus investigational pidnarulex, which inhibits RNA polymerase I–mediated ribosomal RNA synthesis and may stabilize DNA G-quadruplexes.
ClinicalTrials.gov ID: NCT07137416
TrialFetch AI summary: Adults with progressing, measurable pancreatic, prostate, breast, or ovarian cancer and a germline BRCA2 and/or PALB2 mutation receive IV CX-5461 (pidnarulex), an investigational DNA G-quadruplex stabilizer; an exploratory cohort includes patients with high-grade ovarian, fallopian tube, or primary peritoneal cancer and BRCA1 or other HRD-associated alterations. CX-5461 is given on days 1 and 8 of each 28-day cycle, with no control arm.
ClinicalTrials.gov ID: NCT04890613
