[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"ccrcc\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:ccrcc":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,51,81,121,148],{"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":24,"conditions":25,"keywords":35,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":39,"lastUpdatePostDateStruct":40,"startDateStruct":43,"completionDateStruct":45,"leadSponsor":47,"locationsCount":50},"100616025","phase-1-open-label-phase-12-study-of-neo-811-in-subjects-with-locally-advanced-or-metastatic-non-resectable-clear-cell-renal-cell-carcinoma-100616025",false,"NCT07300241","Open-Label Phase 1\u002F2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma","An Open-Label, First-in-Human, Phase 1\u002F2 Dose Escalation and Expansion Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma","Inclusion Criteria:\n\n* Subjects with locally advanced or metastatic non-resectable clear cell renal cell carcinoma (ccRCC).\n* Subjects must have progressed on or refused standard therapies.\n* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.\n* Estimated life expectancy, in the judgment of the Investigator, of at least 12 weeks.\n* Formalin-fixed paraffin-embedded (FFPE) tumor tissue, newly obtained or archival, is mandatory for enrollment to the study.\n* Measurable disease as defined by RECIST v1.1.\n* Adequate hematologic, hepatic, and renal function defined as:\n\n  * Hemoglobin ≥10 g\u002FdL,\n  * Absolute neutrophil count ≥1000 cells\u002FµL,\n  * Platelet count ≥100,000\u002FµL,\n  * AST and ALT ≤2.5 × ULN, or AST and ALT ≤5 × ULN for subjects with liver metastases,\n  * Total bilirubin ≤1.5 × ULN,\n  * Estimated glomerular filtration rate (eGFR) ≥60 mL\u002Fmin.\n* Subject can swallow oral medications and does not have a condition that could impair the oral bioavailability of the study drug.\n* Other inclusion criteria per protocol.\n\nExclusion Criteria:\n\n* Non-clear cell predominant RCC histologic subtypes.\n* Leptomeningeal disease or symptomatic active CNS metastases with exceptions for asymptomatic treated CNS metastases per protocol.\n* Prior or concurrent malignancies with exceptions per protocol.\n* History of hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.\n* Other exclusion criteria per protocol.","ALL","18 Years",{"count":19,"type":20},30,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The NEO-811-101 study is an open-label, first-in-human, Phase 1\u002F2 dose escalation and expansion study testing NEO-811, an ARNT molecular glue degrader, in subjects with locally advanced or metastatic non-resectable clear cell renal cell carcinoma. The study will test NEO-811 initially as a monotherapy.",[26,27,28,29,30,31,32,33,34],"Clear Cell Renal Cell Carcinoma","Renal Cell Carcinoma","RCC","Clear Cell Renal Cell Carcinoma Metastatic","ccRCC","VHL-Associated Clear Cell Renal Cell Carcinoma","VHL-Associated Renal Cell Carcinoma","Kidney Cancer Metastatic","Kidney Cancers",[30,27,26,36,37],"VHL","Kidney Cancer","RECRUITING","2026-05-29",{"date":41,"type":42},"2026-06-02","ACTUAL",{"date":44,"type":42},"2025-12-19",{"date":46,"type":20},"2027-09",{"name":48,"class":49},"Neomorph, Inc","INDUSTRY",10,{"id":52,"slug":53,"hasResults":11,"nctId":54,"briefTitle":55,"officialTitle":56,"acronym":57,"eligibilityCriteria":58,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":59,"targetDuration":4,"studyType":21,"phases":61,"briefSummary":63,"conditions":64,"keywords":66,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":70,"lastUpdatePostDateStruct":71,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":80},"100589038","phase-2-68ga-nym096-pet-ct-for-the-detection-of-ccrcc-in-presurgical-patients-with-complex-cystic-renal-leision-100589038","NCT06949215","68Ga-NYM096 PET\u002F CT for the Detection of ccRCC in Presurgical Patients With Complex Cystic Renal Leision","68Ga-NYM096 PET\u002F CT for the Detection of Clear Cell Renal Cell Carcinoma in Presurgical Patients With Complex Cystic Renal Leision","NYCRCCL","Inclusion Criteria:\n\n1. Age ≥ 18 y\n2. Presence of complex renal cyst (Bosniak category II or higher)\n3. Scheduled for surgical resection of renal mass (partial or total nephrectomy, open, laparoscopic, or robot-assisted technique)\n4. Expected survival of at least 3 months\n5. ECOG ≤ 2\n6. Written informed consent provided for participation in the trial\n7. In the opinion of investigator, willing and able to comply with required study procedures.\n\nExclusion Criteria:\n\n1. On VEGF TKI treatment less than 1 week before 68Ga-NYM096 PET\u002FCT. TKI is known to affect girentuximab binding in patients with ccRCC and is expected to have the same effect on 68Ga-NYM096. If patients were on VEGF TKI treatment, such as sunitinib, sorafenib, cabozantinib, pazopanib, or lenvatinib, a washout of one week before 68Ga-NYM096 PET\u002FCT is required.\n2. Intercurrent medical condition that renders the patient ineligible for surgery.\n3. Pregnancy or breastfeeding.\n4. Severe claustrophobia.",{"count":60,"type":20},70,[62],"PHASE2","This is a prospective, single-center, single-arm, diagnostic phase 2 study aimed at evaluating the sensitivity and specificity of 68Ga-NYM096 PET\u002FCT in detecting clear cell renal cell carcinoma (ccRCC) in patients with complex renal cysts who are scheduled for surgical resection. The study will use histopathological diagnosis as the reference standard to assess the diagnostic accuracy of 68Ga-NYM096 PET\u002FCT in identifying ccRCC within operable complex renal cystic lesion. The findings will provide critical insights into the performance of 68Ga-NYM096 PET\u002FCT as a non-invasive imaging tool for the preoperative detection of ccRCC in this patient population.",[30,65],"Complex Renal Cyst",[67,68,69],"PET\u002FCT","complex renal cyst","68Ga-NYM096","2026-05-21",{"date":72,"type":42},"2026-05-26",{"date":74,"type":42},"2025-05-01",{"date":76,"type":20},"2027-07-01",{"name":78,"class":79},"Peking Union Medical College Hospital","OTHER",1,{"id":82,"slug":83,"hasResults":11,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":87,"eligibilityCriteria":88,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":89,"targetDuration":4,"studyType":21,"phases":91,"briefSummary":93,"conditions":94,"keywords":100,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":112,"lastUpdatePostDateStruct":113,"startDateStruct":115,"completionDateStruct":117,"leadSponsor":119,"locationsCount":5},"100608132","phase-3-phase-3-study-to-assess-safety-and-efficacy-of-177lu-tlx250-in-advanced-relapsed-or-recurrent-ccrcc-100608132","NCT07197580","Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC","A Phase 3, Randomized, Multi-Center, Open-Label Study to Compare 177Lu-TLX250 (Lutetium (177Lu) Girentuximab Tetraxetan) With the Investigator's Choice of a Single Agent Therapy in Participants With Carbonic Anhydrase 9 (CAIX) Expressing, Advanced Relapsed or Recurrent Clear Cell Renal Cell Carcinoma (ccRCC)","LUTEON","Inclusion Criteria:\n\n* be aged ≥ 18 years.\n* have provided written informed consent, dated and signed by the participant prior to any study-specific procedure;\n* have relapsed or recurrent, locally advanced, or metastatic RCC with histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer Staging Manual (Edge SB et al., 2017), with or without sarcomatoid features;\n* have received at least 2 and no more than 3 prior lines of systemic therapies for locally advanced or metastatic ccRCC including a PD-1\u002FPD-L1 inhibitor (at least 2 administrations) and a VEGF\u002FVEGFR-targeting agent (including TKI or mAb) in sequence or in combination;\n* have had radiographic disease progression occurring during or after the most recent line of therapy or intolerance to most recent line of therapy;\n* have at least one measurable lesion according to RECIST, version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions;\n* be CAIX-positive at Screening defined as having at least 1 lesion with a tumor-lesion CAIX ratio of the maximum standardized uptake value (SUVmax) to liver mean standardized uptake value SUVmean) ≥ 1.5 as determined by BICR of 89Zr-TLX250 PET outcomes;\n* have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1;\n* have recovered from the AEs related to prior lines of therapy or returned to baseline with the exception of Grade 2 neurotoxicity. Ongoing, controlled AEs, such as hypothyroidism or hypertension, are permitted;\n* have adequate organ function, defined as:\n* Bone Marrow:\n\n  * leukocytes ≥ 3,000\u002FµL;\n  * absolute neutrophil count ≥ 1500\u002FµL (administration of granulocyte colony stimulating factor is not allowed within 4 weeks prior to the first administration of 177Lu-TLX250;\n  * platelets ≥ 100,000\u002FµL (platelet transfusion is not allowed within 4 weeks prior to the first administration of 177Lu-TLX250); and\n  * hemoglobin ≥ 9g\u002FdL (red blood cell transfusion is not allowed within 2 weeks prior to the first administration of 177Lu-TLX250).\n* Liver Function:\n\n  * total bilirubin ≤ 1.5 × the upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤ 3 × ULN is permitted; and\n  * alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5.0 × ULN for participants with liver metastases.\n* Renal Function:\n\n  * creatinine clearance ≥ 40 mL\u002Fmin as measured by Cockroft-Gault formula or directly calculated by 24h urine;\n  * have negative pregnancy test for women of childbearing potential (serum); and\n\nExclusion Criteria:\n\n* have any of the following:\n\n  * visceral metastatic lesions that are ≥ 1 cm that have a CAIX TLR \\\u003C 1;\n  * lytic bone metastatic lesions with a soft tissue component of at least 1 cm with a TLR \\\u003C 1; and\u002For\n  * at least one metastatic lymph node lesion with short axis ≥ 2.5 cm with a TLR \\\u003C1;\n* received prior 177Lu-TLX250 therapy, any other radioligand therapy, or any prior CAIX-targeting therapy;\n* have any known hypersensitivity to compounds of similar chemical or biologic composition to girentuximab, DFO or DOTA linker, zirconium or lutetium, and\u002For any excipient in the study drug or radiographic contrast-agents;\n* has received G-CSF or erythropoietin within 4 weeks prior to laboratory evaluations at Screening;\n* be currently receiving or have received:\n\n  * any radionuclide within 10 half-lives of the radionuclide prior to 89Zr-TLX250 administration;\n  * any type of systemic anticancer therapy within 2 weeks before the first administration of 177Lu-TLX250;\n  * prior radiotherapy within 2 weeks prior to the first administration of 177Lu-TLX250 (must have recovered from all radiation-related toxicities and not currently require steroid treatment); and\u002For\n  * prior palliative radiation (≤2 weeks of radiotherapy) within 1-week of the first administration of 177Lu-TLX250 for non-central nervous system disease; NOTE: If the investigator feels that the patient is continuing to receive some clinical benefit from standard-of-care (SOC) therapy, the patient may continue SOC therapy up until 2 weeks prior to dosing with 177Lu-TLX250.\n* have known brain metastases, unless these have been treated and stabilized for at least 4 weeks prior to the first administration of 177Lu-TLX250; Note: Participants with a history of brain metastases must have either a head CT with contrast-or brain MRI performed at Screening to document stable disease prior to the first administration of 177LuTLX250.\n* Have experienced any major trauma including major surgery (such as abdominal\u002F cardiac\u002Fthoracic surgery) within 3 weeks of administration of the first administration of 177LuTLX250;\n* be pregnant or intend to become pregnant, breastfeed, or conceive a child during the study period and for at least 42 days after last administration of 89Zr-TLX250 or 6 months after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;\n* Note: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 10.4).\n* be planning to breastfeed during the study period and for 28 days after last administration of 89ZrTLX250 or 75 days after last administration of 177Lu-TLX250, depending on which study drug is administered last to the respective participant;\n* have active and uncontrolled infections requiring systemic therapy or other severe concurrent disease, which, in the opinion of the investigator, would place the participant at undue risk or interfere with the study;\n* have a history of concurrent malignancy with a life expectancy of ≤ 2 years or requirement of systemic anti-cancer therapy or requirement of local therapy that would confound study results; however; participants with the following malignancies can be enrolled into the study:\n\n  * basal cell or squamous cell carcinoma of the skin;\n  * carcinoma in situ of the cervix, breast or bladder; and\u002For\n  * incidental histologic finding of prostate cancer;\n* have a serious, non-healing wound, ulcer, or bone fracture;\n* be unable to stay in the scanner bed with the arms resting out of the thoracic and abdominal fields (i.e., arms alongside the body or raised arm position) for the duration of the scan;\n* have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, and\u002For stable Grade 2 sensory neuropathy, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0;\n* have inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, etc.);\n* have a life expectancy shorter than 3 months;\n* have bleeding or thrombotic disorders or subjects at risk for severe hemorrhage;\n* have experienced any clinically significant bleeding, including hemoptysis or tumor bleeding within 2 weeks prior to the first administration of 177Lu-TLX250;\n* has evidence of a serious active or sub-clinical infection or angina pectoris (New York Heart Association \\[NYHA\\] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, that might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment; or\n* have any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in a clinical study.",{"count":90,"type":20},40,[92],"PHASE3","Multicenter Phase 3 study of 177Lu-TLX250 in adult participants with CAIX-expressing advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC). Part 1 will evaluate two dosing regimens to determine the recommended Phase 3 dose (RP3D). Part 2 will compare 177Lu-TLX250 with investigator's choice of monotherapy aligned with Australian standard-of-care.",[30,95,96,97,98,99],"Renal Cell Carcinoma (Kidney Cancer)","Renal Cell Carcinoma (RCC)","Renal Cell Cancer Metastatic","Renal Cell Cancer, Recurrent","Clear Cell Renal Cell Cancer (ccRCC)",[101,102,37,30,103,104,105,106,107,108,109,110,111],"Carbonic anhydrase 9","Clear Cell Renal Cell Cancer","CA9","CA-9","CAIX","Girentuximab","CA9 target therapy","Positron-Emission Tomography","Radiation Therapy","Radiopharmaceuticals","Targeted Radiation","2026-03-26",{"date":114,"type":42},"2026-04-01",{"date":116,"type":42},"2026-03-25",{"date":118,"type":20},"2029-02-28",{"name":120,"class":49},"Telix Pharmaceuticals (Innovations) Pty Limited",{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":127,"eligibilityCriteria":128,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":129,"targetDuration":4,"studyType":21,"phases":130,"briefSummary":131,"conditions":132,"keywords":134,"overallStatus":138,"whyStopped":4,"lastUpdateSubmitDate":139,"lastUpdatePostDateStruct":140,"startDateStruct":142,"completionDateStruct":144,"leadSponsor":146,"locationsCount":80},"100598868","phase-2-caix-petct-for-residual-or-recurrent-post-ablative-ccrcc-100598868","NCT07077083","CAIX PET\u002FCT for Residual or Recurrent Post-ablative ccRCC","A Pilot Study of 89Zr-girentuximab for PET Imaging in Residual or Recurrent Post Ablative Tumors in Patients With Renal Cell Carcinoma.","CAIX PET\u002FCT","Inclusion Criteria:\n\n1. Written and voluntarily given Informed Consent\n2. ≥18 years of age at time of consent\n\n   a. Because no dosing or adverse event data are currently available on the use of 89Zr-girentuximab in participants \\\u003C18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.\n3. Have the capacity to understand the study and be willing and able to comply with all protocol requirements.\n4. Findings suspicious for post-ablation residual or recurrent ccRCC (subjects in cohort 1) documented at conventional imaging or biopsy, performed within 90 days prior to 89Zr-girentuximab PET scan.\n5. Findings suspicious for primary ccRCC (subjects in cohort 2) documented at standard histology or conventional imaging, performed within 90 days prior to 89Zr-girentuximab PET scan.\n6. Negative serum or urine pregnancy tests in female patients of childbearing potential within 72 hours prior to receiving 89Zr-girentuximab. Female patients of non-child bearing potential must provide evidence by fulfilling one of the following criteria at screening:\n\n   1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\n   2. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution\n   3. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation\n7. For all participants, consent to practice double-barrier contraception until a minimum of 42 days after 89Zr-girentuximab administration.\n\nExclusion Criteria:\n\n1. Renal mass known to be a metastasis of another primary tumor.\n2. Active non-renal malignancy requiring therapy during and up to EOT visit.\n3. Planned antineoplastic therapies (for the period between IV administration of 89Zr-girentuximab and imaging).\n4. Previous administration of any radionuclide within 10 of its half-lives before 89Zr-girentuximab injection day.\n5. Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune, or metabolic), that may interfere with the objectives of the program or with the safety or compliance of the subject, as judged by the Investigator.\n6. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the program.\n7. Women who are pregnant or breastfeeding.\n8. Known hypersensitivity to girentuximab or DFO (desferoxamine).\n9. Renal insufficiency with estimated glomerular filtration rate eGFR ≤ 40 mL\u002Fmin\u002F 1.73 m²",{"count":50,"type":20},[62],"The goal of this clinical trial is to learn whether 89Zr-Girentuximab PET scans can inform management of renal cell carcinoma. The main questions it aims to answer are:\n\n* Does the 89Zr-Girentuximab PET detect ccRCC that is left behind or has come back after treatment?\n* What differences can be seen on the 89Zr-Girentuximab PET before and after standard of care treatment?\n\nParticipants in arm 1 will be given the study drug followed by a PET scan 3-7 days after injection. Participants in arm 2 will receive the same, but will proceed with their standard of care cryoablation after the initial PET scan. Within 3 days of the cryoablation treatment, participants will receive a repeat PET scan.",[133,30],"Clear Cell Renal Cell Carcinoma (ccRCC)",[135,136,137],"kidney","kidney cancer","imaging","NOT_YET_RECRUITING","2026-03-09",{"date":141,"type":42},"2026-03-11",{"date":143,"type":20},"2026-03-16",{"date":145,"type":20},"2028-08-01",{"name":147,"class":79},"Massachusetts General Hospital",{"id":149,"slug":150,"hasResults":11,"nctId":151,"briefTitle":152,"officialTitle":153,"acronym":154,"eligibilityCriteria":155,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":156,"targetDuration":4,"studyType":21,"phases":158,"briefSummary":159,"conditions":160,"keywords":161,"overallStatus":138,"whyStopped":4,"lastUpdateSubmitDate":165,"lastUpdatePostDateStruct":166,"startDateStruct":168,"completionDateStruct":170,"leadSponsor":172,"locationsCount":4},"100628328","phase-2-pembrolizumab-plus-lenvatinib-in-recurrent-ccrcc-patients-failing-permbrolizumab-adjuvant-treatment-100628328","NCT07460206","Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment","Pembrolizumab Plus Lenvatinib in REcurrent ccRCC Patients Failing permbroLizUmab aDjuvant trEatment - PRELUDE Study","PRELUDE","Inclusion Criteria:\n\n* Male or female\n* Age \\>18 years at the time of signing the informed consent\n* Histological confirmation of RCC with a clear-cell component\n* Has locally recurrent\u002Fmetastatic disease (ie, Stage IV per the American Joint Committee on Cancer)\n* Patients with RCC with sarcomatoid features are also allowed in this study\n* Participants must have progressed on treatment with Pembrolizumab administered as adjuvant treatment. Pembrolizumab treatment progression is defined by meeting all of the following criteria:\n\n  1. Has received at least 2 doses of Pembrolizumab as adjuvant treatment\n  2. Has demonstrated disease progression after adjuvant Pembrolizumab as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in Appendix 4).\n  3. Progressive disease has been documented within 12 months from the last dose of adjuvant Pembrolizumab\n  4. Progressive disease is determined according to iRECIST. This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.\n* Male partecipants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose Pembrolizumab and 30 days after last dose of Lenvatinib and agreement to refrain from donating sperm during this period.\n* Female partecipants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last, after the last dose of study treatment and agreement to refrain from donating eggs during this period.\n* Asymptomatic patients with central nervous system (CNS) metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery. Measurable disease must be present outside the CNS. Before protocol enrollment updated CNS imaging with contrast-enhanced brain CT or brain MRI is required for patients who have received CNS-focal treatment (either by surgery or by RT) ≥ 30 days from initiation of protocol treatment.\n* Evaluable International Metastatic RCC Database Consortium (IMDC) risk scores\n* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline, unless adverse events are clinically non significant in the opinion of the investigator. Participants with endocrine related AEs who are adequately treated with hormone replacement are eligible.\n* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial\n* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (KPS \\>70). Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.\n* Have adequate organ function as defined in the following table (Table 4). Laboratory tests must be collected within 14 days prior to the start of study intervention\n* Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150\u002F90 mm Hg with no change in antihypertensive medications within 1 week prior to allocation\n* Ability to comply with protocol requirements\n* The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care\n\nExclusion Criteria:\n\n* Treatment with any anti-cancer therapy as first line therapy after adjuvant therapy with pembrolizumab\n* Adjuvant treatments other than Pembrolizumab\n* Patients with non clear cell RCC\n* Symptomatic, untreated, or actively progressing CNS metastases (patient has no history of intracranial hemorrhage or spinal cord hemorrhage; patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment; no evidence of significant vasogenic edema; patient has no ongoing requirement for corticosteroids as therapy for CNS disease but anticonvulsant therapy at a stable dose is permitted; CNS metastases limited to the cerebellum or the supratentorial region, no metastases to the midbrain, pons, medulla, or spinal cord; no evidence of interim progression between completion of CNS- directed therapy and initiation of study treatment)\n* Has known leptomeningeal disease or carcinomatous meningitis\n* Uncontrolled tumor-related pain symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement; uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures).\n* Moderate to severe hepatic impairment (Child-Pugh B or C)\n* Symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL, or corrected calcium \\> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab\n* History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer\n* Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1. Patients who are receiving single-fraction radiotherapy given for the indication of pain control are eligible\n* Active tuberculosis\n* Major surgical procedure within 3 weeks prior to initiation of study treatment. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. Minor surgeries (e.g., tumor biopsy, placement of vascular access device) should be performed at least 10 days prior to initiation of study treatment. Patients with clinically relevant ongoing complications from prior surgery are not eligible\n* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment\n* Severe infection within 4 weeks prior to initiation of study treatment\n* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment. Administration of killed vaccines is allowed. Note: please refer to Section 5.3.2 for information on COVID-19 vaccines\n* Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment.\n* Treatment with systemic immunosuppressive medication (e.g. corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti.TNF-alfa agents) within 2 weeks prior to initiation of study treatment, with the exceptions for patients who received acute or low dose systemic immunosuppressant medication (e.g. \\>10 mg\u002Fday oral prednisone or equivalent), and patients who received corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency\n* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment\n* Prior allogeneic stem cell or solid organ transplantation\n* Any other disease that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications\n* Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority\n* Concurrent active Hepatitis B (defined as HBsAg positive and\u002For detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection or current treatment with anti-viral therapy for HBV or HCV\n* Active or history of autoimmune disease or immune deficiency (e.g. myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, vasculitis, or glomerulonephritis, multiple sclerosis, psoriatic arthritis) with the exceptions of patients with a history of autoimmune-related hypothyroidism, patients with controlled Type 1 diabetes mellitus who are on an insulin regimen, patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (are eligible provided all of following conditions are met: rash must cover \\\u003C10% of body surface area, disease is well-controlled at baseline and requires only low- potency topical corticosteroids, no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet, radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high- potency or oral corticosteroids within the previous 12 months).\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan\n* Malabsorption syndrome or any other condition that might affect the absorption of lenvatinib.\n* Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.\n* Uncontrolled hypertension defined as sustained blood pressure \\> 150 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment\n* Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).\n* Stroke (including transient ischemic attack), myocardial infarction, or other symptomatic ischemic event, or thromboembolic event within 12 months before randomization, subjects with a diagnosis of incidental PE or DVT within 12 months are allowed if asymptomatic and stable at screening treated with low- molecular-weight heparins or the direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban for at least 1 week before first dose\n* Has urine protein ≥1 g\u002F24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg\u002FdL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria. Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible\n* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.\n* Has a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)\n* History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities\n* History of congenital QT syndrome.\n* QT interval corrected with use of Fridericia's formula (QTcF) \\> 480 ms per ECG within 14 days before randomization\n* Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1.\n* Evidence of bleeding diathesis or significant coagulopathy.\n* Abdominal or tracheoesophageal fistula, bowel obstruction, or gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before initiation of study treatment. Complete healing of an intra abdominal abscess must be confirmed before initiation of study treatment. Has preexisting ≥ Grade 3 gastrointestinal or non-gastrointestinal fistula\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)\n* Clinical signs or symptoms of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding\n* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. NOTE: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage\u002Fnecrosis following lenvatinib therapy\n* Clinically significant hematuria, hematemesis, hemoptysis or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before initiation of study treatment.\n* Serious active ulcer, or untreated bone fracture\n* Prior history of hypertensive crisis or hypertensive encephalopathy\n* Known hypersensitivity to any component of the pembrolizumab formulation. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients. Has discontinued adjuvant Pembrolizumab due to adverse event\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known allergy or hypersensitivity to any component of the lenvatinib formulation\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.",{"count":157,"type":20},108,[62],"This study is being performed as a single-arm open-label study in order to provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with advanced ccRCC who have progressed on Pembrolizumab as their prior therapy in the adjuvant RCC setting.",[30],[162,163,164],"clear cell renal cell carcinoma","Pembrolizumab","lenvatinib","2026-03-03",{"date":167,"type":42},"2026-03-10",{"date":169,"type":20},"2026-08",{"date":171,"type":20},"2031-12",{"name":173,"class":79},"Gruppo Oncologico Italiano di Ricerca Clinica"]