[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"phase-1\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:phase-1":25},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,45,71,92],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":17,"targetDuration":4,"studyType":20,"phases":21,"briefSummary":23,"conditions":24,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100631409","phase-1-phase-1-study-of-sar445877-in-combination-with-folfox6-and-bevacizumab-as-first-line-treatment-for-microsatellite-stable-metastatic-colorectal-cancer-100631409",false,"NCT07500298","Phase 1 Study Of SAR445877 In Combination With FOLFOX6 And Bevacizumab As First-Line Treatment For Microsatellite Stable Metastatic Colorectal Cancer","Eligibility Criteria\n\n1. Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.\n2. Capable of and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study-related tests and procedures.\n3. Age ≥18 years.\n4. Participants with histologically documented CRC with metastatic disease who have not received prior treatment in the metastatic setting. Participants who have received adjuvant FOLFOX must be 6 months from treatment at the time of enrollment.\n5. CRC documented as MSS by immunohistochemistry, next-generation sequencing, or polymerase chain reaction assay at any time prior to screening.\n6. Measurable disease per the RECIST v1.1.\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n8. Adequate organ and marrow function as defined below within 28 days of study treatment initiation:\n\n   * Hemoglobin \\>9.0 g\u002FdL\n   * Absolute neutrophil count ≥1500\u002FmL\n   * Platelets ≥100,000\u002FmL\n   * Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤3 × ULN.\n   * Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤2.5 × institutional ULN. Transaminases up to 3 × ULN in the presence of liver metastases.\n   * Estimated glomerular filtration rate ≥50 mL\u002Fmin\u002F1.73 m² (Modification of Diet in Renal Disease Formula)\n   * For participants not receiving therapeutic anticoagulation: international normalized ratio or activated partial thromboplastin time ≤1.5 × ULN. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen.\n9. Life expectancy ≥ 3 months.\n10. The effects of SAR445877 and FOLFOX\u002Fbevacizumab on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study treatment period, and for 9 months after completion of study treatment.\n\n    (Refer to Pregnancy Assessment Policy MD Anderson Cancer Center \\[MDACC\\] Institutional Policy # CLN1114). WOCBP includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:\n    * Postmenopausal (no menses in ≥12 consecutive months)\n    * History of hysterectomy or bilateral salpingo-oophorectomy\n    * Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range and have received whole pelvic radiation therapy)\n    * History of bilateral tubal ligation or another surgical sterilization procedure\n    * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation or hysterectomy, patient\u002Fpartner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the duration of the study treatment period and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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.\n11. Male participants must agree to use adequate contraception throughout the duration of the study treatment period and for 6 months after the last dose of study treatment\n12. WOCBP must have a negative serum pregnancy test within 3 days prior to first administration of study treatment.\n\nExclusion Criteria\n\n1. Pregnant or breastfeeding.\n2. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that requires\u002Frequired treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. Participants with the following conditions are eligible: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.\n3. Participants who are receiving any other investigational agents.\n4. Receipt of a live-virus vaccination within 28 days prior to study treatment initiation. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to Cycle 1 Day 1 through Cycle 2 Day 3).\n5. Participants with a condition requiring systemic treatment with either corticosteroids (\\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 1 week prior to the first administration of study treatment. Physiologic replacement doses are allowed even if they are \\>10 mg of prednisone\u002Fday or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided they are not for the treatment of an autoimmune disorder. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are eligible to be enrolled in the study.\n6. Known history of positive test for human immunodeficiency virus or known acquired immunodeficiency syndrome, unless most recent CD4 count exceeds 500 cells\u002Fmm3.\n7. Acute or chronic hepatitis B virus or hepatitis C virus infection.\n8. Previous solid organ or allogeneic hematopoietic stem cell transplant.\n9. Active brain or leptomeningeal metastases.\n10. Active infection requiring IV antibiotics or other uncontrolled intercurrent illness requiring hospitalization.\n11. History of interstitial lung disease or severe obstructive pulmonary disease.\n12. Clinically significant cardiovascular\u002Fcerebrovascular disease.\n13. Left ventricular ejection fraction \\\u003C50% as measured by echocardiogram or multigated acquisition scan.\n14. Serious, non-healing wound, ulcer, or bone fracture.\n15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to first administration of study treatment.\n16. Evidence of bleeding or coagulopathy.\n17. Uncontrolled hypertension (\\>150\u002F100 mmHg).\n18. Urine dipstick of proteinuria \\>2+. Participants with \\>2+ proteinuria on dipstick analysis will undergo a 24-hour urine collection and must demonstrate \\\u003C1.0 g protein\u002F24 hours to be eligible.\n19. Known severe hypersensitivity reactions to monoclonal antibodies, any history of or recent (within 6 months) anaphylaxis.\n20. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.\n21. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.\n\n    \\-","ALL","18 Years",{"count":18,"type":19},41,"ESTIMATED","INTERVENTIONAL",[22],"PHASE1","To learn if SAR445877 in combination with FOLFOX6 and bevacizumab can be safely given to patients with advanced MSS CRC.",[25,26,27,28,29,30,31],"Phase 1","SAR445877","FOlfox6","Bevacizimab","First Line Treatment","Metastatic Colorectal Cancer (CRC)","Microsatellite Stable","RECRUITING","2026-05-29",{"date":35,"type":36},"2026-06-01","ACTUAL",{"date":38,"type":36},"2026-05-20",{"date":40,"type":19},"2032-12-27",{"name":42,"class":43},"M.D. Anderson Cancer Center","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":20,"phases":53,"briefSummary":54,"conditions":55,"keywords":4,"overallStatus":62,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":44},"100637386","phase-1-a-phase1-clinical-trial-evaluating-locoregional-delivery-of-engineered-nk-cells-containing-il13ra-and-egfviii-chimeric-antigen-receptor-car-il-21-secretion-and-deleted-tgf-betar2-and-nr3c1-in-recurrent-glioblastoma-100637386","NCT07579208","A Phase1 Clinical Trial Evaluating Locoregional Delivery Of Engineered NK Cells Containing IL13Ra And EGFvIII Chimeric Antigen Receptor (CAR), IL-21 Secretion And Deleted TGF-BetaR2 And NR3C1 In Recurrent Glioblastoma","Eligibility Criteria\n\n1. Male or female subjects aged ≥ 18 years.\n2. Histologically confirmed supratentorial 2021 World Health Organization recurrent glioblastoma (IDH-wildtype GBM), gliosarcoma, or recurrent IDH-mutant WHO grade 4 astrocytoma, with any prior number of recurrences.\n3. Have received prior radiation and temozolomide therapy.\n4. Single tumor no larger than 5 cm in its greatest diameter.\n5. Karnofsky Performance Status (KPS) score of \\>70.\n6. Has a baseline brain MRI obtained no more than 30 days prior to NK cell infusion\n7. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 x 10\u002FL with absolute neutrophil count (ANC) ≥1.5 x109\u002FL, lymphocyte count ≥ 0.5 x 109\u002FL, platelet count ≥ 100 x 109\u002FL, and Hgb ≥ 9 g\u002F dL (in absence of blood transfusion).\n8. Adequate hepatic function defined by a total bilirubin level . 1.5 \\~ ULN, an AST level ≤ 2.5 x ULN, and an ALT level ≤ 2.5 x ULN, and INR ≤ 1.5.\n9. Adequate renal function defined by creatinine ≤ 1.5 X upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL\u002Fmin for subject with creatinine levels \\> 1.5 X institutional ULN.\n10. Female subject of childbearing potential should have a negative serum pregnancy test. Subjects and their partners must be willing to use effective birth control during the study and for up to 3 months following last administration of NK cells. .\n11. Prior Avastin use is allowed after at least a 12-week washout period.\n12. Agree to sign consent to the long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.\n\nExclusion Criteria\n\n1. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery.\n2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks since last dose of agent administration.\n3. Has known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v5.0), any history of anaphylaxis, within 5 months.\n4. Has a known history of Human Immunodeficiency Virus (HIV) (positive HIV 1\u002F2 antibodies); HTLV1 and\u002For HTLV2; active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected). Participants with prior HBV vaccination (anti-HBs positive, HBsAg negative, anti-HBc negative) will NOT be excluded.\n5. Has a diagnosis of immunodeficiency or is receiving any immunosuppressive therapy (such as tacrolimus, cyclosporine, infliximab) within 7 days prior to study registration.\n6. Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study Day 0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent such as thrombocytopenia or platelets toxicity. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study at the discretion of the treating investigator.\n7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include superficial tumors considered adequately treated locally with curative intent, including but not limited to basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Any exceptions must be discussed with the protocol PI.\n8. Has known Gliomatous meningitis or extracranial disease, or tumor localized primarily to the brainstem or spinal cord\n9. Midline shift greater than 0.5 cm or pending herniation\n10. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma\u002Fatopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Participants receiving epidural steroid injections for pain will be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.\n11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis\n12. Has an active infection requiring systemic therapy or that in the opinion of the PI may interfere with the subject's participation, assessment of experimental treatment toxicity or increase the subject's risk of side effects\n13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate in the opinion of the treating investigator.\n14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit and through 3 months after last dose of the study treatment\n16. Has received a live vaccine within 30 days prior to the first dose of trial treatment\n17. Has a contraindication for undergoing MRIs\n18. Has evidence of bleeding diathesis or coagulopathy\n19. Is on full dose anticoagulants or antiplatelet therapy that cannot be held (full dose depends on the actual anticoagulant)\n20. Has significant hemorrhage on baseline scan defined as \\>1 cm diameter of acute blood\n21. Has received any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant)\n22. Has multifocal disease. Subject has multifocal GBM, defined as discrete sites of contrast enhancing disease without contiguous T2\u002FFLAIR abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2\u002FFLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted.",{"count":52,"type":19},36,[22],"To find the best method of administering NK cells in patients with recurrent glioblastoma.",[25,56,57,58,59,60,61],"NK Cell","IL13Ra","EGFRvIII","Chimera Antigen Receptor (CAR)","NR3C1","Recurrent Glioblastoma","NOT_YET_RECRUITING","2026-05-06",{"date":65,"type":36},"2026-05-12",{"date":67,"type":19},"2026-10-24",{"date":69,"type":19},"2030-07-30",{"name":42,"class":43},{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":20,"phases":79,"briefSummary":80,"conditions":81,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":84,"lastUpdatePostDateStruct":85,"startDateStruct":87,"completionDateStruct":89,"leadSponsor":91,"locationsCount":44},"100598495","phase-1-phase-i-study-of-allogeneic-transforming-growth-factor-beta-receptor-type-2-knockout-cd70-car-nk-cells-in-treatment-refractory-clear-cell-renal-cell-carcinoma-100598495","NCT07072234","Phase I Study of Allogeneic Transforming Growth Factor-beta Receptor Type 2 Knockout CD70 CAR NK Cells in Treatment Refractory Clear Cell Renal Cell Carcinoma","Eligibility Criteria\n\n* Participants must have histologically confirmed ccRCC that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.\n* Confirmation of CD70 expression ≥ 10% by immunohistochemistry staining of the participants primary renal tumor or a metastatic lesion biopsy specimen will be required for enrollment in the study.\n* Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.\n* Participants must have previously received treatment with at least one ICI and one TKI. Participants must have had unequivocal disease progression on ICI treatment.\n* Age ≥18 years. Because no dosing or adverse event data are currently available on the use of CD70 TGFβR-2 knockout CAR NK cells in Participants \\\u003C18 years of age, children are excluded from this study.\n* Participants must be at least 2 weeks from last cytotoxic chemotherapy, tyrosine kinas inhibitors or other targeted therapies at the time of administration of lymphodepleting chemotherapy.\n* Participants must be at least 3 months from any cell therapy for malignancy.\n* Localized radiotherapy to 1 or more disease sites is allowed prior to the lymphodepleting chemotherapy, provided that there are additional measurable non-irradiated disease sites.\n* Eastern Cooperative Oncology Group performance status 0 or 1 (Performance level as measured by Karnofsky for Participants \\> 16 years of age.\n* Adequate organ function at screening, as defined by the following:\n\n  * Renal: Serum creatinine ≤ 1.5 mg\u002FdL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥30 ml\u002Fmin\u002F1.73 m2o Hepatic: alanine transaminase (ALT)\u002Faspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg\u002FdL or ≤ 3.0 mg\u002FdL for Participants with Gilbert's Syndrome. No history of liver cirrhosis.\n  * Cardiac: Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)\n  * Pulmonary: No clinically significant pleural effusion (per principal investigator \\[PI\\] judgement), and baseline oxygen saturation ≥ 92% on room air. Subjects with active interstitial lung disease (ILD)\u002Fpneumonitis requiring treatment with systemic steroids will be excluded.\n* Hematological: absolute neutrophil count (ANC) ≥ 1000\u002Fmm3, platelet count ≥ 75,000\u002Fmm3, and hemoglobin ≥ 8 g\u002FdL.\n\n  o Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Participants on therapeutic doses of anticoagulation medication must have INR and\u002For aPTT ≤ the upper limit of the therapeutic range for intended use.\n* Able to provide written informed consent.\n* Aged ≥18 years.\n* Weight ≥40 kg.\n* All male and female Participants who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy. Acceptable forms of birth control for female Participants include: hormonal contraception (implant, injectable contraceptive, transdermal patch, vaginal ring), intrauterine device, tubal ligation or hysterectomy, subject\u002Fpartner post vasectomy, diaphragm with spermicide, condom with spermicide, or abstinence. Female Participants who become pregnant or suspect pregnancy must immediately notify their doctor. Female Participants who become pregnant will be taken off study. Men who are able to have children must use effective birth control while on the study therapy. Acceptable forms of birth control for male Participants include: vasectomy, condom with spermicide or abstinence. If the male Participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.\n* Negative serum or urine beta human chorionic gonadotropin pregnancy test for females of childbearing potential (defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females) at screening.\n* Signed consent to long-term follow-up on protocol PA17-0483 and lab protocols PA17-0577 and LAB02-152.\n\nExclusion Criteria\n\n* Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated withthe previous anticancer treatment, as determined by the PI. Toxicities related to priorsurgery, radiation, prior systemic immune checkpoint inhibitors and chemotherapy should be resolved to Grade 1 or below prior to lymphodepletion.\n* Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note: Participants with simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.\n* Known active hepatitis B or C.\n* Known human immunodeficiency virus (HIV).\n* Presence of active neurological disorder(s).\n* Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).\n* Amyloidosis or POEMS syndrome.\n* Symptomatic or uncontrolled central nervous system involvement or signs of cord compression. In the case radiation therapy is indicated, the washout must be at least 14 days.\n* Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post resection or post radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-life-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the Participant's ability to participate and\u002For complete this trial. Examples include but are not limited to urothelial cancer Grade Ta or T1 and adenocarcinoma of the prostate treated by active surveillance.\n* Presence of any other serious medical condition that may endanger the Participant at investigator's discretion, including but not limited to:\n* New York Heart Association Class III or IV heart failure\n* Myocardial infarction or stroke ≤ 26 weeks prior to CAR NK cell infusion\n* Unstable angina within ≤ 13 weeks prior to CAR NK cell infusion unless the underlying disease has been corrected by procedural intervention (e.g., stent, bypass)\n* Severe aortic stenosis\n* Uncontrolled arrhythmia. PI approval is required for Participants with arrhythmia who may be included as an exception.\n* Congenital long QT syndrome. PI approval is required.\n* Documentation, during the screening process, of a QTc \\> 470 milliseconds by Fredericia criteria (QTcF) based on the average of 3 electrocardiograms (ECGs) taken approximately 1 minute apart and all within 10 minutes of each other. The patient should be reclining for 5 minutes prior to ECGs. Local readings may be used for this exclusion criterion.\n* Major surgery \\\u003C 4 weeks prior to first dose of lymphodepleting chemotherapy.\n* Concomitant use of other investigational agents.\n* Concomitant use of other anticancer agents.\n* Participants receiving systemic steroid therapy at time of enrollment, with an exception for topical, ocular, intranasal, and inhaled corticosteroids, or systemic corticosteroids at an equivalent dose ≤ 10 mg of prednisone daily (physiological substitutive doses are allowed).\n* Received antithymocyte globulin within 14 days or alemtuzumab within 28 days of enrollment.\n* Participants receiving immunosuppressive therapy.\n* Pregnant or breastfeeding.\n* Has received a live vaccine within 6 weeks prior to CAR NK cell infusion. Examples of live vaccines include but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virusvaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.",{"count":78,"type":19},30,[22],"Testing an investigational cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy.",[82,25,83],"Clear Cell Carcinoma","Growth Factor","2026-04-28",{"date":86,"type":36},"2026-04-29",{"date":88,"type":36},"2025-09-25",{"date":90,"type":19},"2030-02-01",{"name":42,"class":43},{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":96,"acronym":4,"eligibilityCriteria":97,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":98,"targetDuration":4,"studyType":20,"phases":100,"briefSummary":101,"conditions":102,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":105,"lastUpdatePostDateStruct":106,"startDateStruct":108,"completionDateStruct":110,"leadSponsor":112,"locationsCount":44},"100566841","phase-1-phase-1-dose-escalation-and-expansion-study-of-prame-t-cell-receptor-tcr-engineered-nk-cells-in-participants-with-recurrent-andor-refractory-melanoma-prametime-mel-100566841","NCT06660420","Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and\u002For Refractory Melanoma (PRAMETIME-Mel)","Inclusion Criteria:\n\n1. Participants must be 18 years or older.\n2. Participants must be willing and able to provide informed consent.\n3. Participants must have HLA A\\*02:01.\n4. Participants must have histologically documented locally advanced, unrespectable, or metastatic melanoma that is relapsed and\u002For refractory to immune checkpoint inhibitor (ICI) therapy including either anti-PD-1 either with or without anti-CTLA-4 blocking antibody and\u002For anti-LAG-3 antibody.\n\n   During dose escalation, participants with cutaneous, mucosal, or unknown primary melanoma will be enrolled. Participants with uveal melanoma may be eligible for future enrollment into distinct cohorts during the dose confirmation phase. Participants should have received standard-of-care (SOC) therapy per standard clinical practice guidelines. Participants must not have had exposure to more than 3 prior lines of anti-PD-1 antibody-containing therapeutic regimens administered in the metastatic setting.\n5. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n6. Life expectancy 3 months.\n7. Participants who received one or more prior systemic therapy are allowed for enrollment\n8. A female participant is eligible to participate if at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidelines in during the study treatment period and for 6 months post PRAME-TCR-NK cell infusion. Female participants who become pregnant or suspect pregnancy must immediately notify their doctor.\n\n   Female participants who become pregnant will be taken off the study.\n9. Male participants must agree to follow the contraceptive guidelines during the study treatment period and for 6 months post PRAME-TCR-NK cell infusion. Male participants who father a child or suspect that they have fathered a child must immediately notify their doctor.\n10. WOCBP must have a negative urine pregnancy test within 72 hours before the start of lymphodepleting chemotherapy. If a WOCBP has a urine pregnancy test that cannot be confirmed as negative, a serum (beta-human chorionic gonadotropin \\[£\\]-hCG\\]) pregnancy test will be required.\n11. Participants must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST).\n12. Participants must have adequate organ function as defined below within 10 days before the start of lymphodepleting chemotherapy:\n13. Left ventricular ejection fraction \\>50%.\n14. Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and baseline oxygen saturation \\>92% in room air.\n15. Willing to undergo mandatory blood collection and biopsies as required by the study.\n16. Participants must agree not to receive a live vaccine for at least 24 months post-infusion.\n17. Willing to sign consent for long-term follow-up on protocol PA17-0483 which will be signed at the same time with the clinical trial enrollment consent form.\n\nExclusion Criteria:\n\n1. Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post PRAME-TCR-NK cell infusion.\n2. Has received systemic anticancer therapy within 2 weeks or 5 half-lives, whichever is shorter, before the start of lymphodepleting chemotherapy. For participants treated with monoclonal antibodies, at least 3 weeks must have elapsed before the start of lymphodepleting chemotherapy. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.\n3. Participants must have recovered from all AEs due to previous therapies to . Grade 1 or baseline. Participants with Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI)\u002Fco-PIs. If a with . Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI)\u002Fco-PIs. If a participant received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention before the start of lymphodepleting chemotherapy.\n4. Has received prior radiotherapy within 2 weeks of the start of lymphodepleting chemotherapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (2 weeks of radiotherapy) to non-CNS disease.\n5. Has received a live vaccine within 6 weeks prior to PRAME-TCR-NK infusion. Examples of live vaccines include but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.\n6. Has a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding10 mg daily of prednisone equivalent).\n7. History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.\n8. Known active CNS metastases and\u002For carcinomatous meningitis. Patients with previously treated brain metastases may participate if they completed radiation therapy, are clinically stable, and without the requirement of steroid treatment for at least 2 weeks prior to study enrollment.\n9. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.\n10. Need for systemic immunosuppressive therapy or other physiological replacement of corticosteroids.\n11. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.\n12. Active infection (e.g., COVID-19, influenza, severe acute respiratory syndrome \\[SARS\\], recent sepsis). For participants recovered from infections, lymphodepletion may start after full recovery.\n13. Known human immunodeficiency virus (HIV) infection, active or chronic hepatitis B or hepatitis C virus infection.\n14. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participants participation for the full duration of the study, or is not in the best interest of the participants to participate, in the opinion of the treating investigator.\n15. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.\n16. Has had an allogeneic tissue\u002Fsolid organ transplant.\n17. Clinically significant cardiovascular disease within 12 months before the start of lymphodepleting chemotherapy, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebrovascular event, or cardiac arrhythmia associated with hemodynamic instability. NOTE: A medically controlled arrhythmia would be permitted.\n18. Prolongation of corrected QT interval using Fridericia's formula to \\>480 milliseconds.\n19. Participants with bleeding or thrombotic disorders or at risk for severe hemorrhage. Participants with a known history of deep vein thrombosis\u002Fpulmonary embolism who are on appropriate anti-coagulation treatment are eligible.\n20. Participants with LDH \\> 2.5-fold ULN. The evaluation should be conducted at screening.\n\n    \\-",{"count":99,"type":19},39,[22],"To find the highest tolerable dose and recommended dose of PRAME-TCR-NK cells that can be given to participants with recurrent and\u002For refractory melanoma. The safety and tolerability of PRAME-TCR-NK cells will also be studied.",[25,103,104],"Recurrent Melanoma","Refractory Melanoma","2026-04-13",{"date":107,"type":36},"2026-04-16",{"date":109,"type":36},"2025-02-25",{"date":111,"type":19},"2031-12-31",{"name":42,"class":43}]