[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"squamous-cell-carcinoma-of-larynx\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:squamous-cell-carcinoma-of-larynx":31},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,55],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":36,"overallStatus":42,"whyStopped":4,"lastUpdateSubmitDate":43,"lastUpdatePostDateStruct":44,"startDateStruct":47,"completionDateStruct":49,"leadSponsor":51,"locationsCount":54},"100450377","phase-1-rapa-201-therapy-of-solid-tumors-100450377",false,"NCT05144698","RAPA-201 Therapy of Solid Tumors","Phase I\u002FII Trial of Autologous Rapamycin-Resistant Th1\u002FTc1 (RAPA-201) Cell Therapy of PD-(L)1 Resistant Solid Tumors","Inclusion Criteria:\n\n1. Male or female patients ≥ 18 years of age.\n2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n3. Advanced metastatic, recurrent, and unresectable solid tumor that has relapsed after ≥ one prior line of therapy.\n4. Subject must have received prior therapy with disease-specific regimens that have been established to convey a clinical benefit. Alternatively, subject must have been offered such regimens and provided written documentation of refusal to receive such regimens.\n5. Subject with solid tumors with genetic alterations and mutations (including but not limited to BRAF, BRCA, EGFR mutations, and ALK translocations) must have either received targeted therapy for such conditions or provided written documentation of refusal to receive such regimens.\n6. Exposure to an anti-PD-(L)1 monoclonal antibody therapeutic in the most recent line of prior therapy.\n7. Documented refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody, as defined by lack of response after at least two cycles of therapy or relapse within 12-months of initiation of anti-PD-(L)1-containing therapy.\n8. Solid tumor disease types that are eligible for enrollment consist of:\n\n   1. head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites);\n   2. malignant melanoma;\n   3. small cell carcinoma, thoracic and extra-thoracic; and,\n   4. non-small cell lung cancer.\n9. Presence of measurable disease to permit monitoring by RECISTv1.1 Criteria.\n10. Must have a potential source of autologous T cells potentially sufficient to manufacture RAPA-201 cells, as defined by a circulating absolute lymphocyte count (ALC) of ≥ 300 cells\u002FμL.\n11. Patients must be ≥ two weeks from last solid tumor cancer chemotherapy, major surgery, radiation therapy and\u002For participation in investigational trials.\n12. Patients must have recovered from clinical toxicities (resolution of CTCAE (v5) toxicity to a value of ≤ 2).\n13. Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal limits, with an EF level of ≥ 40%.\n14. Calculated creatinine clearance of ≥ 60 mL\u002Fmin\u002F1.73 m\\^2.\n15. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal.\n16. ANC (Absolute neutrophil count) of ≥ 1500 cells\u002FμL.\n17. Platelet count ≥ 100,000 cells\u002FμL.\n18. Hemoglobin count ≥ 8 grams\u002FμL.\n19. Bilirubin ≤ 1.5 mg\u002FdL (except if due to Gilbert's disease).\n20. Corrected DLCO ≥ 50% (Pulmonary Function Test)\n21. No history of abnormal bleeding tendency (as defined by any inherited coagulation defect, or history of internal bleeding).\n22. 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\n1. Other active malignancy (except non-melanoma skin cancer).\n2. Life expectancy \\\u003C 4 months.\n3. Seropositivity for HIV, hepatitis B, or hepatitis C, unless such conditions are in stable condition using adequate treatment.\n4. Uncontrolled hypertension.\n5. History of cerebrovascular accident within 6 months of enrollment.\n6. Myocardial infarction within 6 months prior to enrollment.\n7. NYHA class III\u002FIV congestive heart failure.\n8. Uncontrolled angina\u002Fischemic heart disease.\n9. Cancer metastasis to the central nervous system, unless such metastasis has been adequately treated.\n10. Pregnant or breastfeeding patients.\n11. Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.\n12. Patients may be excluded at the discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.","ALL","18 Years",{"count":19,"type":20},37,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct immune therapy treatment platform for solid tumors. The administration of polyclonal, metabolically-fit RAPA-201 cells is a novel adoptive T cell therapy approach that is suitable for regenerative medicine efforts.\n\nRAPA-201 is a novel immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1\u002FTc1 cytokine phenotype. RAPA-201, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. The novel RAPA-201 manufacturing platform, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1\u002FTc1 polarizing agent (IFN-alpha) generates polyclonal T cells with five key characteristics:\n\n1. Th1\u002FTc1: polarization to anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets;\n2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence for prolonged anti-tumor effects;\n3. Rapamycin-Resistance: acquisition of rapamycin-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment;\n4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and\n5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment.\n\nThis is a non-randomized, open label, multi-site, phase I\u002FII trial of outpatient RAPA-201 immune T cell therapy in patients with advanced metastatic, recurrent, and unresectable solid tumors that have recurred or relapsed after prior immune therapy. Patients must have tumor relapse after at least one prior line of therapy and must have refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody. Furthermore, accrual focuses upon solid tumor disease types potentially amenable to standard-of-care salvage chemotherapy consisting of the carboplatin + paclitaxel (CP) regimen that will be utilized for host conditioning prior to RAPA-201 therapy. Importantly, carboplatin and paclitaxel are \"immunogenic\" chemotherapy agents whereby the resultant cancer cell death mechanism is favorable for generation of anti-tumor immune T cell responses. Thus, the CP regimen that this protocol incorporates is intended to directly control tumor progression and indirectly promote anti-tumor T cell immunity.\n\nProtocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered in the outpatient setting every 28 days (chemotherapy administered on cycles day 1, 8, and 15). RAPA-201 cells will be administered at a target flat dose of 400 X 10\\^6 cells per infusion on day 3 of cycles 2 through 6.\n\nIn the original protocol design, a sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual consisted of n=10 patients; to advance to the second protocol accrual stage (accrual of an additional n=12 patients), RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients. As described below in the detailed description, this original protocol implementation demonstrated that RAPA-201 represented an active treatment regimen for solid tumor patients, and as such, the protocol was expanded to evaluate the combination of RAPA-201 therapy followed by anti-PD1 maintenance therapy.",[27,28,29,30,31,32,33,34,35],"Solid Tumor","Small Cell and Non-small Cell Lung Cancer","Head and Neck Cancer","Squamous Cell Carcinoma of Oral Cavity","Squamous Cell Carcinoma of Larynx","Squamous Cell Carcinoma of Nasopharynx","Squamous Cell Carcinoma of Other Specified Sites of Skin","Malignant Melanoma","Esophageal Squamous Cell Carcinoma",[37,38,39,40,41],"Refractory to Checkpoint Therapy","PD-1","PD-L1","Adoptive T cell therapy","Regenerative Medicine","RECRUITING","2025-05-09",{"date":45,"type":46},"2025-05-14","ACTUAL",{"date":48,"type":46},"2021-08-01",{"date":50,"type":20},"2026-12-31",{"name":52,"class":53},"Rapa Therapeutics LLC","INDUSTRY",1,{"id":56,"slug":57,"hasResults":11,"nctId":58,"briefTitle":59,"officialTitle":60,"acronym":61,"eligibilityCriteria":62,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":63,"enrollmentInfo":64,"targetDuration":4,"studyType":21,"phases":66,"briefSummary":67,"conditions":68,"keywords":80,"overallStatus":42,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":100},"100526640","phase-2-european-larynx-organ-preservation-study-elos-mk-3475-c44-100526640","NCT06137378","European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]","ELOS - Induction Chemotherapy With Docetaxel and Cisplatin Followed by Radiation Compared to Additional PD-1 Inhibition in CPS ≥1 Advanced Laryngeal\u002FHypopharyngeal Cancer Suitable for Laryngectomy Selected After Early Response Evaluation","ELOS","Inclusion Criteria:\n\nParticipants are eligible to be included in the study only if all of the following criteria apply:\n\n1. Male and female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of squamous cell carcinoma (SCC) of the larynx or hypopharynx according to the decision of the multidisciplinary tumor board suitable for total laryngectomy can be enrolled in this study.\n2. Stage III, IVA or IVB, whenever clear resection margins R0 \\>5 mm can be achieved and no radiologic signs of extranodal extension of neck nodes are present.\n3. Have provided newly obtained excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.\n4. PD-L1-expression\\* within the tumor biopsy, CPS ≥1\n5. Male participants:\n\n   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 of study treatment and refrain from donating sperm during this period.\n6. 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) OR\n   2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.\n7. 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 date of allocation\u002Frandomization.\n8. Have adequate organ function as defined in the (Table 4) of the protocol. Specimens must be collected within 10 days prior to the start of study treatment.\n\nExclusion Criteria:\n\nParticipants are excluded from the study if any of the following criteria apply:\n\n1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of study medication (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory receptor on T or NK cells (e.g., CTLA-4, OX 40, CD137).\n3. Has received prior systemic anti-cancer therapy including investigational agents.\n4. Has received prior radiotherapy.\n5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.\n6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.\n7. 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.\n8. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.\n9. Has known distant metastases including active CNS metastases and\u002For carcinomatous meningitis.\n10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients.\n11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with 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, etc.) is not considered a form of systemic treatment and is allowed.\n12. Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease.\n13. Has an active infection requiring systemic therapy.\n14. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.\n15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.\n16. Has a known history of active TB (Bacillus Tuberculosis).\n17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n19. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.\n20. Has had an allogenic tissue\u002Fsolid organ transplant.\n21. Has a known intolerance to one of the substances administered during treatment including e.g. antibiotics, antiemetics, etc. or any other component of concurrent auxiliary medication.","70 Years",{"count":65,"type":20},140,[24],"ELOS is a prospective, randomized, open-label, controlled, two-armed parallel group, phase II multicentre trial in local advanced stage III, IVA\u002FB head and neck squamous cell carcinoma of the larynx or hypopharynx (LHNSCC) with PD-L1-expression within tumor tissue biopsy, calculated as CPS ≥ 1 curable by total laryngectomy. Induction chemotherapy (IC) with Docetaxel and Cisplatin (TP) followed by radiation will be compared to additional PD-1 inhibition. Patients will be selected after short induction early response evaluation after the first cycle IC (IC-1) aiming on larynx organ-preservation by additional 2 cycles IC followed by radiotherapy (69.6 Gy) for responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥ 30%. Nonresponders (ETSS \\\u003C 30% or progressing disease) will receive total laryngectomy and selective neck dissection followed by postoperative radiation or chemoradiation according to the recommendation of the clinics multidisciplinary tumor board. However, Patients randomized into the intervention arm starting day 1 will receive 200 mg Pembrolizumab (MK-3475) i.v. in 3-week cycle (q3w) for 17 cycles (12 months). Treatment with pembrolizumab will continue in the experimental arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent from subsequent decision on adjuvant therapy after TL.",[69,70,71,72,31,73,74,75,76,77,78,79],"Squamous Cell Carcinoma of Head and Neck","Hypopharyngeal Squamous Cell Carcinoma","Laryngeal Squamous Cell Carcinoma Stage III","Laryngeal Squamous Cell Carcinoma Stage IV","Squamous Cell Carcinoma of the Larynx","Squamous Cell Carcinoma of the Larynx Stage III","Squamous Cell Carcinoma of the Larynx Stage IV","Laryngeal Squamous Cell Carcinoma","Laryngectomy; Status","Laryngeal Cancer","Laryngeal Neoplasms",[81,82,83,84,85,86,87,88,89],"induction chemotherapy","neoadjuvant treatment","immune checkpoint inhibitor","pembrolizumab","KEYNOTE","larynx organ preservation","laryngectomy-free survival","overall survival","event-free survival","2024-09-18",{"date":92,"type":46},"2024-09-20",{"date":94,"type":46},"2024-04-17",{"date":96,"type":20},"2030-12",{"name":98,"class":99},"University of Leipzig","OTHER",9]