[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Grupo Español Multidisciplinar de Melanoma\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":125},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,44,74,100],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":27,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":5},"100597369","phase-2-neoadjuvant-tebentafusp-in-patients-with-metastatic-uveal-melanoma-100597369",false,"NCT07057596","Neoadjuvant Tebentafusp in Patients With Metastatic Uveal Melanoma","NEO-TB","Inclusion Criteria:\n\n1. Patients must have histologically confirmed metastatic uveal melanoma with Human leukocyte antigen-A\\*0201 positive determined by local assay.\n2. Patients with histologically proven metastatic uveal melanoma in the liver with reectable or potentially resectable liver metastases evaluated by imaging in a multidisciplinary committee. Metastasis can be considered resectable by any of the following:\n\n   1. Minor resection (i.e., less than a hemihepatectomy)\n   2. Major resection (i.e., hemihepatectomy or extended hepatectomy)\n   3. Bilobar resection (including atypical resection).\n3. Must meet the following criteria related to prior treatment:\n\n   1. No prior systemic therapy in the metastatic or advanced setting including chemotherapy, immunotherapy, or targeted therapy.\n   2. No prior local, liver-directed therapy including chemotherapy, radiotherapy, radiofrequency ablation (RFA), or embolization.\n   3. Prior neoadjuvant or adjuvant therapy is allowed provided it was administered in the curative setting in patients with localized disease.\n4. Institutional Review Board (IRB)\u002FIndependent Ethics Committee (IEC) approved written and signed informed consent.\n5. Male or female patients age ≥ 18 years of age at the time of informed consent.\n6. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-1\n7. Adequate organ function as defined below (without transfusion):\n\n   1. Hemoglobin ≥9.0 g\u002FdL.\n   2. Absolute neutrophil count (ANC) \\>1.5 x 109\u002FL (\\> 1500 per mm3).\n   3. Platelet count ≥ 100 x 109\u002FL (\\>75,000 per mm3).\n   4. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the Coordinating Investigator.\n   5. Both AST and ALT must be \\\u003C 5 x ULN.\n   6. Creatinine clearance ⩾50 ml\u002Fmin calculated by Cockcroft-Gault (Table 4) or another validated method.\n   7. Potassium, magnesium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) \\> grade 1.\n\nExclusion Criteria:\n\n1. Presence of extrahepatic disease.\n2. Patients with concomitant malignancy other than non-melanoma skin cancer, or superficial bladder cancer controlled with local treatment. Patients with prior malignancy must have been disease free for 5 years.\n3. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies.\n4. Clinically significant cardiac disease or impaired cardiac function, including any of the following:\n\n   1. Clinically significant and\u002For uncontrolled heart disease such as congestive heart failure (New York Heart Association grade ≥ 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment.\n   2. QTcF \\> 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome.\n   3. Acute myocardial infarction or unstable angina pectoris \\\u003C 6 months prior to Screening.\n5. History of adrenal insufficiency.\n6. History of interstitial lung disease\n7. History of pneumonitis that required corticosteroid treatment or current pneumonitis\n8. History of colitis or inflammatory bowel disease.\n9. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug.\n10. Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations.\n11. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated.\n12. Previous treatment with Tebentafusp.\n13. Patients receiving systemic steroid therapy or any other immunosuppressive medication at any dose level. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable.\n14. Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary).\n15. Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to the start of study drug. Patients must have completed therapy with hematopoietic colony-stimulating factor at least 2 weeks before the first dose of study drug is given. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent.\n16. Hypersensitivity to the active substance of tebentafusp or to any of its excipients, including: Citric acid monohydrate (E330) Di-sodium hydrogen phosphate (E339) Mannitol (E421) Trehalose Polysorbate 20 (E432).\n17. Patients whose circumstances will not permit study completion or adequate follow up.\n18. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation).\n19. Women of child-bearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment, and must agree to continue using such precautions for 1 week after the final dose of investigational product. Highly effective methods of contraception are described in Appendix 5.\n20. Male patients must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 1 week following administration of the last dose of study drug.","ALL","18 Years",{"count":19,"type":20},19,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","Uveal melanoma (UM) is a rare type of melanoma, with an incidence of 4.4 cases per million in Europe each year. During recent years, different treatment approaches have been tested in patients with metastatic UM. Responses have been reported primarily with localized treatment in patients with a limited number of liver metastases. In cases of diffuse liver involvement or extrahepatic disease, systemic therapies are justified. However, to date, systemic therapies such as targeted therapy with selumetinib or conventional chemotherapy have failed in metastatic UM.\n\nNeo-TB is a Phase II, single arm, multicentre clinical trial designed to evaluate efficacy and safety of tebentafusp used as a single agent in patients with metastatic uveal melanoma with resectable \u002F potentially resectable liver metastasis and absence of extrahepatic disease.\n\nThe main questions it aims to answer are:\n\n1. Which is the capacity of tebentafusp used as a single agent to generate pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable liver metastasis and absence of extrahepatic disease.\n2. Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse \u002F progression.\n3. Which is the safety of tebentafusp used as a single agent in metastatic uveal melanoma.\n\nThe main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable\u002Fpotentially resectable liver metastasis and absence of extrahepatic disease. It is assumed that untreated patients would not present a pCR (response rate of ≤1%).",[26],"Mestastatic Uveal Melanoma",[28,29,30,31],"Melanoma","Tebentafusp","Metastatic","Neoadjuvant","RECRUITING","2026-03-05",{"date":35,"type":36},"2026-03-06","ACTUAL",{"date":38,"type":36},"2025-07-18",{"date":40,"type":20},"2027-12",{"name":42,"class":43},"Grupo Español Multidisciplinar de Melanoma","OTHER",{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":50,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":21,"phases":54,"briefSummary":55,"conditions":56,"keywords":59,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":65,"lastUpdatePostDateStruct":66,"startDateStruct":68,"completionDateStruct":70,"leadSponsor":72,"locationsCount":73},"100584265","phase-2-encorafenib-and-binimetinib-followed-by-cemiplimab-and-fianlimab-in-patients-with-braf-mutant-melanoma-and-symptomatic-brain-metastases-100584265","NCT06887088","Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases","Phase II, Single Arm, Multicentre Clinical Trial to Evaluate the Activity of Encorafenib Plus Binimetinib Followed by Cemiplimab And Fianlimab in Patients With BRAF Mutated Melanoma and Symptomatic Brain Metastases","ENCEFALO","Inclusion Criteria:\n\nPatients eligible for inclusion in this study must meet all the following criteria:\n\n* Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.\n* Histologically confirmed diagnosis of unresectable metastatic BRAF-mutated melanoma (stage IV, AJCC v9), with one or more brain metastases with a diameter of 5 to 50 mm, measured by contrast enhanced MRI.\n* Patients with brain metastasis that debut as symptomatic, regardless of corticosteroid use. The definition of symptoms will be:\n\n  1. Any symptom related with intracranial hypertension, providing the patient has an Eastern cooperative Oncology Group performance status (ECOG PS) 0-2 and the other inclusion and exclusion criteria are met.\n  2. Any symptom related to focal neurologic deficit.\n  3. Epilepsy Note: Patients could have or not these symptoms controlled with corticosteroids at the inclusion of the clinical trial.\n* A documented mutation in BRAF-V600 in the tumor tissue.\n* Modified Barthel Index of Activities of Daily Living \\> 10 (see Appendix 5).\n* Subjects aged ≥ 18 years.\n* Performance status ECOG PS 0-2 (see Appendix 7).\n* Able to swallowing\n* Adequate hematologic function:\n\n  1. Haemoglobin ≥ 9 g\u002FdL (may have been transfused).\n  2. Platelet count ≥ 75 × 109\u002FL.\n  3. Absolute neutrophil count (ANC) ≥ 1.5 × 109\u002FL.\n* Adequate hepatic function defined by a total bilirubin level ≤ 2.0 × the upper limit of normality (ULN) and AST and ALT levels ≤ 2.5 × ULN; or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).\n* Serum Creatinine ≤ 2.0 x ULN or estimated creatinine clearance ≥ 30 mL\u002Fmin according to the Cockcroft-Gault formula (or local institutional standard method).\n* Immunotherapy allowed if administered in the adjuvant\u002Fneoadjuvant setting, any grade 3-4 prior toxicity must be resolved to grade 0 or at baseline levels.\n\nSteroids or anticonvulsants are allowed if clinically needed. No dose limit of steroids is pre-specified as long as they are not in an increasing dose for the last 5 days prior to start of study treatment.\n\n\\- Female subjects of childbearing potential (WOCBP) must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%; refer to Appendix 8) for the duration of the study treatment and for 6 months after the last dose of study treatment.\n\nA woman is considered of childbearing potential ( i.e. fertile) following menarche and until becoming postmenopausal unless permanently sterile. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n1. Amenorrheic for ≥1 year in the absence of chemotherapy and\u002For hormonal treatments\n2. Luteinizing hormone (LH) and\u002For follicle stimulating hormone and\u002For estradiol levels in the postmenopausal range\n3. Radiation induced oophorectomy with last menses \\>1 year ago\n4. Chemotherapy induced menopause with \\>1 year interval since last menses\n5. Surgical sterilization (bilateral oophorectomy or hysterectomy)\n6. Women \\\u003C50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\n7. Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n\n   * Male study participants with WOCBP partners are required to use condoms during the study and until 6 months after the last dose of study treatment unless they are vasectomized or practice sexual abstinence.\n   * WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment. All men must agree not to donate sperm during the trial and for 6 months after receiving the last therapy dose.\n   * Willingness and ability to attend scheduled visits, follow the treatment schedule and undergo clinical tests and other study procedures.\n\nExclusion Criteria:\n\nPatients meeting any of the following criteria are excluded from the study:\n\n* Uveal melanoma.\n* History of leptomeningeal metastases unless they are a finding in the Brain MRI that does not explain the main neurological symptoms of the patient, according to physician criteria.\n* Another non-cured cancer in the last 2 years, except for in situ carcinoma of the cervix, breast, prostate or squamous cell carcinoma of the skin adequately treated or limited basal cell skin cancer adequately controlled. Patients with cured cancer should be free of any adjuvant treatment (i.e chemotherapy or targeted therapy\u002Fmonoclonal antibodies) with the exception of hormonal therapy for completed cured localized breast cancer or localized prostate cancer.\n* History of allogeneic organ transplant.\n* History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease (RDD).\n* History of interstitial lung disease.\n* Systemic immunotherapy treatment for melanoma would be allowed only in the adjuvant\u002Fneoadjuvant setting (regardless if the brain relapse was during or after that) providing that ALL the following criteria are met:\n\n  1. The immunotherapy regimen did not contain anti LAG-3 treatment.\n  2. Patient did not have brain metastases (whether they were symptomatic or asymptomatic) prior to this adjuvant\u002Fneoadjuvant immunotherapy setting.\n  3. Patient was treated with adjuvant\u002Fneoadjuvant for at least 6 months.\n  4. No other treatments different than the one in adjuvant\u002Fneoadjuvant before symptomatic brain metastases were applied.\n  5. Patient did not discontinue immunotherapy due to related adverse events.\n* Targeted therapy against BRAF and\u002For MEK will not be allowed in any setting, including adjuvant.\n* Chemotherapy will not be allowed in any setting.\n* Patients in the need of urgent brain surgery before inclusion. However, patients are allowed to enter in the clinical trial after brain surgery, providing they meet the rest of inclusion and exclusion criteria, especially having at least one measurable lesion as per modified RECIST criteria after this surgery.\n* Brain radiotherapy will not be allowed before entering the clinical trial. Patients can receive brain radiotherapy during the clinical trial, if they progress into the brain, as per institutional guidelines ONLY if (must fulfill the three):\n\n  1. They have received at least TWO doses of cemiplimab and fianlimab AND\n  2. The event of an intracranial progressive disease happens during cemiplimab and fianlimab AND\n  3. They comply to receive encorafenib and binimetinib as rechallenge. Encorafenib and binimetinib should be stopped 24h before, during and 24h after radiotherapy.\n* History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.\n* Active infection requiring therapy.\n* Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.\n* Uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.\n\nNotes:\n\n1. Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.\n2. Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.\n3. Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.\n4. Patients with HIV or hepatitis must be reviewed by a qualified specialist (eg, infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial.\n\n   * Impaired cardiovascular function or clinically significant (i.e., active) cardiovascular diseases such as: cerebrovascular accident\u002Fstroke (\\\u003C 6 months prior to enrolment), myocardial infarction (\\\u003C 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), a LVEF \\\u003C 50% evaluated as per institutional guidelines, or serious cardiac arrhythmia requiring medication or a triplicate average baseline QTc interval \\> 500 ms, history of myocarditis.\n\nNote: Patients not fulfilling these cardiovascular criteria can be consulted to medical monitor and coordinating investigator for a case by case examination.\n\n* TnT or troponin I TnI \\> 2x institutional ULN at baseline. Note: Patients with TnT or TnI levels between \\> 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are \\> 1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgment in the patient's best interest.\n* Uncontrolled arterial hypertension despite medical treatment.\n* Moderate (Child Pugh Class B) or severe (Child Pugh Class C) hepatic impairment.\n* Impairment of gastrointestinal function. Inability to swallow tablets or capsules.\n* Neuromuscular disorders associated with high concentrations of creatine kinase.\n* Subjects that have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 weeks (28 days) prior to the first dose of trial treatment, other than steroids required for brain metastasis symptoms control.\n* History of pneumonitis within the last 5 years.\n* Active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis).\n* Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.\n* Known hypersensitivity to the active substances or to any of the excipients.\n* Persisting toxicity related to prior therapy of Grade \\>1 NCI-CTCAE v 5.0; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable.\n* Have received a live vaccine within 30 days of planned start of study therapy. Note: Live or live attenuated vaccination with replicating potential. If a patient intends to receive a COVID-19 vaccine before the start of study drug, participation in the study should be delayed at least 1 week after any COVID-19 vaccination. During the treatment period, it is recommended to delay COVID-19 vaccination until patients are receiving and tolerating a steady dose of study drug. A vaccine dose should not be less than 48 hours before or after study drug dosing.\n* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 6 months after the last dose of study treatment.\n* Known alcohol or drug abuse.\n* Participation in any interventional drug or medical device study within 30 days prior to treatment start.\n* Total lactase deficiency or glucose-galactose malabsorption.",{"count":53,"type":20},33,[23],"Brain metastases in patients with advanced and metastatic melanoma are a frequent complication and a significant cause of morbidity and mortality in this patient population. As the incidence of brain metastases continues to increase in patients with metastatic melanoma, it is urgent that the investigators identify effective therapies.\n\nENCEFALO is a Phase II, single arm, multicentre clinical trial designed to evaluate the activity of encorafenib plus binimetinib followed by cemiplimab and fianlimab in patients with BRAF mutated melanoma and symptomatic brain metastases, following the simon design Two-stage minimax.\n\nThe objective main is to evaluate the 6 month intracranial progression-free survival (icPFS) proportion of Encorafenib plus Binimetinib followed by Cemiplimab plus Fianlimab in patients with BRAF-mutated melanoma and symptomatic brain metastases according RECIST criteria\n\nThe trial hypothesis is: For patients with BRAF-mutated melanoma and symptomatic brain metastases, an induction treatment with encorafenib and binimetinib (EB) for about two months (i.e. 8 weeks) followed by cemiplimab plus fianlimab (CF) would allow a 6 month icPFS rate of 40% in comparison to historical control of 20% based on CM204 symptomatic arm (Tawbi et al 2021).",[57,58],"Melanoma BRAF V600E\u002FK Mutated","Melanoma and Brain Metastases",[28,60,61,62,63,64],"Encorafenib","Binimetinib","Cemiplimab","Fianlimab","BRAF mutant","2025-09-26",{"date":67,"type":36},"2025-10-01",{"date":69,"type":36},"2025-05-29",{"date":71,"type":20},"2028-01",{"name":42,"class":43},18,{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":82,"targetDuration":4,"studyType":21,"phases":84,"briefSummary":85,"conditions":86,"keywords":87,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":94,"completionDateStruct":96,"leadSponsor":98,"locationsCount":99},"100585780","phase-2-plug-in-pembrolizumab-combined-with-enfortumab-vedotin-for-advanced-melanoma-patients-100585780","NCT06906822","PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients","A Phase II, Open-label, Multicenter, Non-Randomized Study of the Efficacy and Safety of Enfortumab Vetodin in Combination With Pembrolizumab Previously Treated Advanced Melanoma","PlugIN","Inclusion Criteria:\n\nParticipants are eligible to be included in the study only if all of the following criteria apply:\n\n1. Male\u002Ffemale participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of unresectable or metastatic melanoma will be enrolled in this study.\n2. Participants must have measurable disease by investigator assessment according to RECIST v1.1 Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy.\n3. Male participants:\n\n   a. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for 9 months after last dose of EV or 4 months after pembrolizumab, whichever occurs last; and refrain from donating sperm during this period.\n4. Female participants:\n\n   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:\n   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3. OR\n   2. WOCBP should remain on contraception for 12 months after the last dose of EV or 4 months after pembrolizumab, whichever occurs last.\n5. Participants must have received prior systemic therapy for locally advanced or metastatic melanoma:\n\n   a. Participants must have progressed on treatment with an anti-PD-1\u002FL1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria: i. Has received at least 2 doses of an approved anti-PD-1\u002FL1 mAb.\n   * Has demonstrated disease progression after anti-PD-1\u002FL1 as defined by RECIST v1.1.\n   * 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.\n\n   ii. Progressive disease \u002F recurrence has been documented within 12 weeks from the last dose of anti-PD-1\u002FL1 mAb. 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\n   b. BRAF mutated patients should have received BRAF\u002FMEK inhibitors and PD1\u002FPDL1 therapy c. Prior CTLA4 therapy is allowed.\n6. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.\n\n   Note: Patients who had cutaneous adverse events grade 3 or superior are not eligible for the study.\n7. Provide representative formalin-fixed paraffin-embedded\u002FFFPE paraffin block obtained after last treatment progression. Patients who have no archival tumor tissue after the last treatment progression will be required to provide a fresh biopsy, if the procedure is feasible and safe for the patient. Older archival tumor samples are allowed for patients with no recent archival tissue (after last treatment progression) and not capable of undergoing a new tumor biopsy before the first dose of study treatment.. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.\n8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.\n9. Have adequate organ function as defined in the following table (see Table 3 in protocol). Specimens must be collected within 10 days prior to the start of study intervention.\n\nExclusion Criteria:\n\n1. Participants are excluded from the study if any of the following criteria apply:\n\n   A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n2. Participants who have previously received enfortumab vedotin or other MMAE-based ADCs.\n3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the scheduled date of starting the study treatment.\n4. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.\n\n   Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.\n5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.\n6. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n7. Participants with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \\\u003C8% with associated diabetes symptoms that are not otherwise explained.\n8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n9. Known additional malignancy that is progressing or has required active treatment within the past 2 years.\n\n   Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.\n10. Has known active CNS metastases and\u002For carcinomatous meningitis. Note: Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.\n11. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients. Participants with known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20).\n12. Participants with active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.\n13. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)\n14. Participants with conditions requiring systemic doses of corticosteroids (\\>10 mg\u002Fday of prednisone or equivalent) or other immunosuppressive medications are excluded.\n15. Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required corticosteroids or has current pneumonitis\u002Finterstitial lung disease.\n16. Has an active infection requiring systemic therapy.\n17. Has a known history of Human Immunodeficiency Virus (HIV) infection.\n18. 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.\n\n    Note: Hepatitis B and C screening tests are not required unless:\n\n    Known history of HBV and HCV infection As mandated by local health authority\n19. Has not adequately recovered from major surgery or has ongoing surgical complications.\n20. 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.\n21. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n22. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of contraception period.\n23. Has had an allogenic tissue\u002Fsolid organ transplant.\n24. History of Clinical Tuberculosis",{"count":83,"type":20},60,[23],"There is a lack of strategies for patients who progress after responding to PD-1\u002Fl-1 in melanoma. High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas. The combination of enfortumab\u002Fvedotin (EV) and pembrolizumab has shown synergistic effect in various solid tumors. Enfortumab vedotin and pembrolizumab may have a dual effect on clinical outcomes.\n\nPLUGIN is a multicenter, non-randomized open-label, 2-cohort, phase 2 study to evaluate the ORR of pembrolizumab in combination with enfortumab vedotin (EV) in previously treated participants with unresectable stage III or IV melanoma and disease progression on standard therapy.\n\nThe primary objective is evaluate the efficacy of enfortumab\u002Fvedotin and pembrolizumabplus pembrolizumab in advanced melanoma.\n\nHypothesis: 1) High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas; 2)EV+Pembrolizumab has shown synergistic effect in various solid tumors; 3) There is a lack of strategies for patients who respond to PD1-mAbs in melanoma.\n\nPrimary Endpoint: Objective Response Rate (ORR) as assessed by the investigator according RECIST 1.1\n\nA total of 60 patients will be enrolled in this study to evaluate efficacy and outcomes in two different cohorts:\n\nCohort 1: patients who did not have BRAF mutation V600E and had disease progression on immune (IO) therapy.\n\nCohort 2, patients with activating BRAF mutations, must have progressed on IO therapy and BRAF\u002FMEKi",[28],[28,88,89,90],"Enfortumab","vedotin","pembrolizumab","2025-09-16",{"date":93,"type":36},"2025-09-18",{"date":95,"type":36},"2025-06-10",{"date":97,"type":20},"2028-06",{"name":42,"class":43},13,{"id":101,"slug":102,"hasResults":11,"nctId":103,"briefTitle":104,"officialTitle":104,"acronym":105,"eligibilityCriteria":106,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":107,"targetDuration":109,"studyType":110,"phases":4,"briefSummary":111,"conditions":112,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":116,"lastUpdatePostDateStruct":117,"startDateStruct":119,"completionDateStruct":121,"leadSponsor":123,"locationsCount":124},"100332246","descriptive-observational-study-on-the-characteristics-of-advanced-and-metastatic-melanoma-in-spain-100332246","NCT03605771","Descriptive Observational Study on the Characteristics of Advanced and Metastatic Melanoma in Spain","GEM-1801","Inclusion Criteria:\n\n* Patients of legal age with stage III, metastatic, or unresectable melanoma at first diagnosis after January 8, 2018. First diagnosis is understood as: a. Disease onset as metastatic or unresectable disease; b. First metastatic or unresectable relapse in the pre-established dates (after January 8, 2018) in a patient with previous localised melanoma and completely resected on dates before the pre-inclusion period.\n* Signing the Informed Consent Form (ICF).\n* A patient may have received the first or subsequent treatments for metastatic or unresectable disease in a hospital other than the centre where the ICF was signed, as long as the patient meets the inclusion criteria 1.\n* A patient can only sign one ICF (cannot sign an ICF in two different centres).\n* If a patient signs the ICF in a centre during the first-line therapy and then goes to another centre with consideration for the following lines: If the centre is associated with the GEM-1801 study, researchers will do their best to update the following lines and the patient status, introducing the new information in the centre where the ICF was initially signed. This information will be provided by the patient before contacting the principal investigator and always with prior consent of the patient, who will have previously provided the consent to contact by telephone for this purpose. If this second (or subsequent) centre is not associated with the GEM- 1801 study, this will be considered loss of follow-up, unless the patient returns to the GEM-1801 start centre, wherein the reporting physicians will do their best to update the information from other centres, always with prior patient consent, who will have previously signed the ICF; c) A patient card with the assigned code will be delivered.\n\nExclusion Criteria:\n\n* Any patient not complying with inclusion criteria.",{"count":108,"type":20},400,"24 Months","OBSERVATIONAL","This is an observational, multicentre epidemiological study with a longitudinal cohort in which information will be retrieved from medical records of patients with advanced metastatic or unresectable melanoma at first diagnosis.",[113,114,115],"Melanoma Stage Iv","Melanoma Stage Iii","Advanced Cancer","2025-04-02",{"date":118,"type":36},"2025-04-04",{"date":120,"type":36},"2018-08-07",{"date":122,"type":20},"2025-12",{"name":42,"class":43},39,""]