[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"unresectable-colorectal-adenocarcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:unresectable-colorectal-adenocarcinoma":31},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,45],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100604262","phase-1-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-100604262",false,"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","A Phase 1 and Randomized Phase 2 Trial of Pidnarulex (CX-5461) and Cemiplimab (REGN2810) in Refractory Microsatellite Stable Colorectal Cancer","Inclusion Criteria:\n\n* Patients must have pathologically confirmed colorectal adenocarcinoma that is unresectable and\u002For metastatic and for which standard curative or palliative measures do not exist or are no longer effective\n* Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1\n* Patients must have pathologically confirmed proficient mismatch repair proteins (pMMR) and\u002For not microsatellite-high status (non-MSI-H). This may be confirmed by local tissue testing of the primary tumor and\u002For any metastatic lesion utilizing approved immunohistochemistry (for mismatch repair status) and\u002For 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\u002For MSI testing may be performed on that tissue if not done previously. Clinical documentation of the patient's MMR and\u002For MSI status in the medical record may also be utilized to determine MMR and\u002For 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\n* Phase 2 patients must have at least one liver metastasis at study entry (by imaging and\u002For histology, per investigator assessment); this metastasis does not need to be measurable\n* Phase 2 patients must have local\u002Fstandard of care tumor molecular testing (tumor tissue or circulating tumor DNA) demonstrating MYC amplification or deleterious\u002Flikely deleterious FBXW7 mutation, as defined in the report\n* Phase 2 patients must have at least one tumor lesion amenable to biopsy\n* Patients must undergo a washout period of 28 days for epidermal growth factor receptor (EGFR) inhibitors, including cetuximab and panitumumab\n* 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\u002Ftipiracil, 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\n* 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 \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Absolute neutrophil count ≥ 1,500\u002FmcL\n* Platelets ≥ 100,000\u002FmcL\n* Hemoglobin ≥ 9 g\u002FdL\n* 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\u002Fdl may be enrolled)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × institutional ULN, (5 × ULN for patients with liver involvement)\n* Glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* 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\n* 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\n* 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\n* 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\n* 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\u002FPD-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\n* 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\n\nExclusion Criteria:\n\n* 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\n* 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\n* Presence of known photosensitivity disorders\n\n  * 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\n* 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)\n* 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\n* Patients who are receiving any other investigational agents\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pidnarulex (CX-5461) and cemiplimab\n* 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\n* 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\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* 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)","ALL","18 Years",{"count":19,"type":20},86,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","This phase I\u002FII 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\u002For effective in treating patients with refractory MSS CRC.",[27,28,29,30,31],"Metastatic Colorectal Adenocarcinoma","Refractory Colorectal Adenocarcinoma","Stage III Colorectal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","Unresectable Colorectal Adenocarcinoma","RECRUITING","2026-06-26",{"date":35,"type":36},"2026-06-29","ACTUAL",{"date":38,"type":20},"2026-12-21",{"date":40,"type":20},"2027-09-30",{"name":42,"class":43},"National Cancer Institute (NCI)","NIH",5,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":21,"phases":54,"briefSummary":55,"conditions":56,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":60,"completionDateStruct":62,"leadSponsor":64,"locationsCount":65},"100569632","phase-1-clinical-trial-of-an-anti-cancer-drug-ca-4948-emavusertib-in-combination-with-chemotherapy-treatment-folfox-plus-bevacizumab-in-metastatic-colorectal-cancer-100569632","NCT06696768","Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer","Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed colorectal adenocarcinoma\n* Patients must have unresectable or metastatic measurable disease on imaging for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determination within 28 days of registration\n* For patients enrolling to the expansion cohort, lesions must be amenable to research biopsy\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CA-4948 (emavusertib) and FOLFOX in combination with bevacizumab in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)\n* Absolute neutrophil count ≥ 1,500\u002FmcL (within 28 days of registration)\n* Platelets ≥ 75,000\u002FmcL (within 28 days of registration)\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (within 28 days of registration)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × institutional ULN; for those with liver metastases, 5 × institutional ULN (within 28 days of registration)\n* Estimated glomerular filtration rate (eGFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 (within 28 days of registration)\n* Creatine phosphokinase (CPK) elevation at screening \\\u003C grade 2 (CPK ≤ 2.5 x ULN) (within 28 days of registration)\n* Patients on a cholesterol lowering statin must be on a stable dose with no dose changes within 3 weeks prior to study start\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* 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\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible, after discussion with the principal investigator (PI) or medical monitor, if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* 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\n* 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\n* Patients must be able to take oral medications\n* The effects of CA-4948 (emavusertib) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of childbearing potential must continue contraception for 9 months following the last dose of study drugs. 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. Males treated or enrolled on this protocol and involved with women of childbearing potential must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months following the last dose of study drugs\n* Patients must have the 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\n\nExclusion Criteria:\n\n* Patients with high-frequency microsatellite instability (MSI-H) or deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) colorectal cancer at pre-enrollment screening\n* Patients with prolonged QT interval by Fridericia's correction formula (QTcF) (\\> 450ms) on screening electrocardiogram (ECG)\n* 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\n* Patients who are receiving any other investigational agents\n* Patients who have received prior treatment with any chemotherapy (either in the adjuvant or metastatic setting), including FOLFOX, fluorouracil\u002Fleucovorin\u002Firinotecan (FOLFIRI), folinic acid\u002Ffluorouracil\u002Foxaliplatin\u002Firinotecan (FOLFOXIRI), or antiangiogenic agents such as bevacizumab and similar agents, are not eligible for this study\n* Patients with a known dihydropyrimidine dehydrogenase deficiency\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 (emavusertib) or other agents used in the study\n* Patients with a gastrointestinal (GI) condition that could impair absorption of CA-4948 (emavusertib) or cause an inability to ingest CA-4948 (emavusertib)\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because CA-4948 (emavusertib) is a blood-brain barrier penetrant with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CA-4948 (emavusertib), breastfeeding should be discontinued if the mother is treated with CA-4948 (emavusertib). These potential risks may also apply to other agents used in this study. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry\n* Patients with a history of allogeneic organ or stem cell transplantation\n* Patients with significant active bleeding or those in whom the treating physician believes bevacizumab would not be safe or appropriate\n* Patients who have had palliative radiation to bone metastases within 2 weeks prior to day 1 of the study treatment\n* Patients who have had a major surgical procedure within 4 weeks prior to day 1 of the study treatment\n* Patients with hypertension not controlled by antihypertensive medication\n* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \\[anti-TNF\\] agents) within 14 days prior to randomization; however,\n\n  * Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of ≤ 10 mg\u002Fday methylprednisolone equivalent) may be enrolled\n  * The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed\n* Severe infections within 28 days prior to registration, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. This includes receipt of oral or IV antibiotics within 14 days prior to registration. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible",{"count":53,"type":20},24,[23],"This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLFOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and\u002For effective in treating patients with metastatic colorectal cancer.",[27,29,30,31],"2026-06-02",{"date":59,"type":36},"2026-06-03",{"date":61,"type":36},"2025-06-23",{"date":63,"type":20},"2026-12-31",{"name":42,"class":43},13]