Testing Pidnarulex and Cemiplimab for Refractory Colorectal Cancer
This study is testing the anti-cancer drugs Pidnarulex (CX-5461) and Cemiplimab (REGN2810) for people with colorectal cancer that has spread (metastatic) or cannot be removed by surgery, and has not responded to other treatments (refractory). Pidnarulex may stop cancer cell growth, and Cemiplimab is an immunotherapy that helps your body's immune system fight cancer. The study aims to find the best dose of Pidnarulex when given with Cemiplimab, and to see how safe and effective this combination is. You may be able to join if you have microsatellite stable (MSS) colorectal cancer and your disease can be measured. The study is looking for 86 participants, but the current recruitment status is unclear.
- Study design
- This is a Phase I/II interventional study involving about 86 participants. It aims to find the best dose and then evaluate the effectiveness of the drugs.
- What's involved
- You would undergo tumor and blood sample collection, and have imaging tests like CT or MRI. The study will assess side effects up to 30 days after your last dose, and progression-free survival for up to 2 years.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your progression-free survival will be assessed for up to 2 years after randomization, or until disease progression or death.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07147231
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
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~86 participants
Updated 2026-08-13 on ClinicalTrials.gov
What's tested:Biopsy ProcedureBiospecimen CollectionCemiplimabComputed TomographyMagnetic Resonance ImagingPidnarulex
At a glance
Recruiting sites
6 of 6 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recommended phase 2 dose (RP2D) of pidnarulex (CX-5461) with anti-programmed cell death protein 1 (anti-PD-1) (Phase 1)
Measured over Up to 28 days
+2 more outcomes measured
Conditions
Where it's being run
6 sites across 3 statesGeorgia3
Maryland2
District of Columbia1
Study leadership
- Wells A Messersmith · PRINCIPAL_INVESTIGATOR · JHU Sidney Kimmel Comprehensive Cancer Center LAO
Who to contact
Site Public Contact
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
Phase 2 patients must have local/standard of care tumor molecular testing (tumor tissue or circulating tumor DNA) demonstrating MYC amplification or deleterious/likely deleterious FBXW7 mutation, as defined in the report
Phase 2 patients must have at least one tumor lesion amenable to biopsy
Patients must undergo a washout period of 28 days for epidermal growth factor receptor (EGFR) inhibitors, including cetuximab and panitumumab
Patients must have progressed on or have intolerance to (if eligible and not contraindicated per treating investigator) fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and epidermal growth factor receptor (EGFR) inhibitor. These are standard of care treatments for this patient population with proven survival benefit, so it would not be appropriate for patients to enroll in this trial without this criterion being met. Subsequent standard of care treatments (trifluridine/tipiracil, fruquintinib, and regorafenib) have a very modest improvement on survival of only a few months compared to placebo and thus clinical trial options are commonly sought after oxaliplatin and irinotecan but before these other agents
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of pidnarulex (CX-5461) in combination with cemiplimab in patients \< 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Absolute neutrophil count ≥ 1,500/mcL
Platelets ≥ 100,000/mcL
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.5 × 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)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN, (5 × ULN for patients with liver involvement)
Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for ≥ 1 month after treatment of the brain metastases
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
The effects of that pidnarulex (CX-5461) on the developing human fetus are unknown. Based on its mechanism of action, cemiplimab (REGN2810) can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. For these reasons, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 14 days prior to study entry, for the duration of study participation and for at least 4 months after the last dose of cemiplimab (REGN2810) and 6 months after the last dose of pidnarulex (CX-5461). Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking cemiplimab (REGN2810) for at least 4 months after cessation of treatment, and for pidnarulex (CX-5461), for 6 months after cessation of treatment. Women should not donate eggs for 14 days prior to the study, for the duration of study participation, and 6 months after completion of pidnarulex (CX-5461) and cemiplimab (REGN2810). Male patients must also agree to not donate sperm for 14 days prior to the study, for the duration of study participation, and 6 months after completion of pidnarulex (CX-5461) and cemiplimab (REGN2810) administration
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion
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
Patients with a history of cicatricial conjunctivitis or active ocular surface disease (as evaluated by ophthalmologist as needed; routine eye exam for all study participants is not needed)
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents
Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pidnarulex (CX-5461) and cemiplimab
Patients who use strong CYP3A4 inhibitors or strong CYP3A4 inducers. Pidnarulex (CX-5461) has been shown to be metabolized primarily by the CYP3A4 enzyme. Inhibitors and substrates of these enzymes can increase pidnarulex (CX-5461) plasma concentrations while inducers of these enzymes can decrease pidnarulex (CX-5461) plasma concentrations
Patients who are taking corticosteroids at a dose greater than 10 mg of prednisone daily or other immunosuppressive or disease-modifying agents, as this may reduce efficacy of an immunotherapy regimen
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant and lactating women are excluded from this study. The exclusion is based on the potential risk of adverse effects of pidnarulex (CX-5461) on fetal development and newborn health. The safety of pidnarulex (CX-5461) 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 (CX-5461), leading to unpredictable drug exposure and efficacy. There is also an increased risk of immune-mediated rejection of the developing fetus with cemiplimab (REGN2810)
What this trial measures
- Recommended phase 2 dose (RP2D) of pidnarulex (CX-5461) with anti-programmed cell death protein 1 (anti-PD-1) (Phase 1)Up to 28 days
The Bayesian optimal interval design will be employed to identify the RP2D of pidnarulex (CX-5461) in combination with anti-PD-1.
- Incidence of adverse events, serious adverse events, and dose limiting toxicitiesUp to 30 days after last dose of study drug
Will evaluate safety and tolerability of pidnarulex (CX-5461) alone and in combination with anti-PD-1 in phases 1-2. Safety and tolerability will be summarized via descriptive statistics, including adverse events, serious adverse events, and dose limiting toxicities.
- Progression-free survival (PFS) (Phase II)From randomization until disease progression (as assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1) or death from any cause, whichever occurs first, assessed up to 2 years
Will evaluate PFS of pidnarulex (CX-5461) alone and in combination with anti-PD-1 in patients with refractory liver metastatic microsatellite stable colorectal cancer associated with replication stress in phase 2. PFS will be compared between the 2 treatment groups following the futility boundary on hazard ratio (HR) derived by using a Hwang-Shih-DeCani spending function with gamma = -2.909. The Kaplan-Meier method will be used to estimate median PFS, PFS rates at different time points, and their 95% confidence intervals (CIs), using the Brookmeyer Crowley's method. The HR and the corresponding two-sided 95% CI will be estimated in a stratified Cox regression model. Stratification factors are consistent with those used at randomization. Subgroup analysis will be performed to assess the consistency of treatment effect across subgroups.