Health Trials

Testing the Effectiveness of the Anti-cancer Drug Pidnarulex (CX-5461), in Combination With Another Anti-cancer Drug Cemiplimab (REGN2810), in Treating Refractory Microsatellite Stable Colorectal Cancer

ConditionsMetastatic Colorectal AdenocarcinomaRefractory Colorectal AdenocarcinomaStage III Colorectal Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Unresectable Colorectal Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase I/II trial studies the side effects and best dose of pidnarulex when given together with cemiplimab and to see how well it works in treating patients with microsatellite stable (MSS) colorectal cancer (CRC) that does not respond to treatment (refractory). Pidnarulex may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pidnarulex with cemiplimab may be safe, tolerable and/or effective in treating patients with refractory MSS CRC.

Eligibility criteria

Qualifiers

Patients must have pathologically confirmed colorectal adenocarcinoma that is unresectable and/or metastatic and for which standard curative or palliative measures do not exist or are no longer effective

Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

Patients must have pathologically confirmed proficient mismatch repair proteins (pMMR) and/or not microsatellite-high status (non-MSI-H). This may be confirmed by local tissue testing of the primary tumor and/or any metastatic lesion utilizing approved immunohistochemistry (for mismatch repair status) and/or polymerase chain reaction or next generation sequencing (for microsatellite status) assays. Historical (i.e., previously obtained) biopsy mismatch repair (MMR) and microsatellite instability (MSI) status may be utilized. If historical tissue is available, MMR and/or MSI testing may be performed on that tissue if not done previously. Clinical documentation of the patient's MMR and/or MSI status in the medical record may also be utilized to determine MMR and/or MSI status for the purposes of eligibility. pMMR results for eligibility testing must be available prior to study enrollment and no eligibility testing will be conducted on study

Phase 2 patients must have at least one liver metastasis at study entry (by imaging and/or histology, per investigator assessment); this metastasis does not need to be measurable

Disqualifiers

Patients with active autoimmune diseases, defined as requiring systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs. Replacement therapy (eg; thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment

Patients with prior treatment with an RNA polymerase inhibitor, G quadruplex stabilizer, or immunotherapy. This includes prior treatment with a PD-1 or PD-L1 inhibitor agent

Presence of known photosensitivity disorders

Patients who do not agree to use sunglasses and sunscreen (≥ sun protective factor (SPF) 50 to ultraviolet B (UVB) and a high degree of protection against ultraviolet A (UVA) if exposed to sunlight during the study and for 4 weeks after the last dose are not eligible. Patients may also not use sun tanning beds during the study, and within 4 weeks after the last dose

Trial design

Treatments tested in this trial

  • Biopsy Procedure
  • Biospecimen Collection
  • Cemiplimab
  • Computed Tomography
  • Magnetic Resonance Imaging
  • Pidnarulex
  • Positron Emission Tomography

Treatment groups

86 Participants
are divided into 3 treatment groups

Locations

5
Emory Saint Joseph's Hospital30342, AtlantaGeorgia, United States
Emory University Hospital Midtown30308, AtlantaGeorgia, United States
Emory University Hospital/Winship Cancer Institute30322, AtlantaGeorgia, United States
Johns Hopkins University/Sidney Kimmel Cancer Center21287, BaltimoreMaryland, United States

Sponsors and collaborators

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov