[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07594067":3,"trial-entities:NCT07594067":114,"trial-summary:NCT07594067":121},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":10,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":22,"study_type":23,"primary_purpose":24,"phases":25,"enrollment_info":27,"interventions":30,"primary_outcomes":49,"secondary_outcomes":62,"sex":84,"minimum_age":85,"maximum_age":16,"healthy_volunteers":86,"eligibility_criteria":87,"std_ages":91,"locations":94,"central_contacts":109,"overall_officials":111,"references":112,"see_also_links":113},"NCT07594067","27225","TCR1188-ABC Cells in KRAS-mutated Cancers","Phase I, Open-Label Study of Autologous Mutant KRAS and ILT4-Redirected T-cell Receptor Cells (TCR1188-ABC)","RECRUITING","2042-07","2026-08","2026-08-06","University of Pennsylvania","OTHER",true,"This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1188-ABC cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or non-small cell lung cancer (NSCLC) will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.",null,[18,19,20,21],"Cholangiocarcinoma","Colorectal Cancer","Non-Small Cell Lung Cancer","Pancreatic Adenocarcinoma",[],"INTERVENTIONAL","TREATMENT",[26],"PHASE1",{"count":28,"type":29},30,"ESTIMATED",[31,40,45],{"type":32,"name":33,"description":34,"armGroupLabels":35},"BIOLOGICAL","TCR1188-ABC cells","TCR1188 modified, base-edited autologous CD4+ and CD8+ T cells expressing TCR1188 and a scFv fragment specific to ILT4 (LILRB2) as a Single infusion on Day 0",[36,37,38,39],"Dose level -1","Dose level 1","Dose level 2","Dose level 3",{"type":41,"name":42,"description":43,"armGroupLabels":44},"DRUG","Fludarabine + Cyclophosphamide combination","Fludarabine: 30 mg\u002Fm2\u002Fday x 4 days (Day -7 to -4) Cyclophosphamide: 600mg\u002Fm2\u002Fday x 3 days (Day -7 to -5)",[36,37,38,39],{"type":41,"name":46,"description":47,"armGroupLabels":48},"Tocilizumab","Single administration of 8mg\u002Fkg on Day 2 (+3d)",[36,37,38,39],[50,54,58],{"measure":51,"description":52,"timeFrame":53},"Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V6.0","Type, frequency, severity, and attribution of adverse events","Up to 15 years following TCR1188-ABC cell administration",{"measure":55,"description":56,"timeFrame":57},"Occurrence of dose-limiting toxicities (DLTs)","Type, frequency, severity, and attribution of dose limiting adverse events as defined by the protocol","Up to 28 days following TCR1188-ABC cell administration",{"measure":59,"description":60,"timeFrame":61},"Identification of the maximum tolerated dose (MTD)","The highest dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects will be declared the MTD.","28 days post-TCR1188-ABC cell infusion",[63,67,70,74,77,80],{"measure":64,"description":65,"timeFrame":66},"Occurrence of product release failures","Calculated based on the proportion of subjects with TCR1188-ABC cell products that fail to meet the product release criteria, out of the number of eligible subjects in whom manufacturing was attempted, will be calculated.","3 months",{"measure":68,"description":69,"timeFrame":66},"Proportion of TCR1188-ABC cells that fail to meet the protocol-defined dose","Proportion of subjects with TCR1188-ABC cell products that fail to meet the assigned dose, out of the number of eligible subjects in whom manufacturing was attempted.",{"measure":71,"description":72,"timeFrame":73},"Overall Response Rate (ORR)","Proportion of subjects with CR or PR as the best overall response as assessed by RECIST 1.1 from the first response assessment post-infusion until the end of the primary follow-up.","Up to 12 months following TCR1188-ABC cells administration",{"measure":75,"description":76,"timeFrame":53},"Duration of Response (DOR)","Duration of time from the date the response criteria of CR or PR is first met, to the date of confirmed disease progression, or the date of the last adequate disease assessment performed before the occurrence of another censoring event.",{"measure":78,"description":79,"timeFrame":53},"Progression-Free Survival (PFS)","Duration of time from the TCR1188-ABC cell infusion to the date of confirmed disease progression or death due to any cause, or the date of the last adequate disease assessment performed before the occurrence of another censoring event.",{"measure":81,"description":82,"timeFrame":83},"Overall Survival (OS)","Time from the first TCR1188-ABC cell infusion to death due to any cause; or censored at the date of last contact.","Up to 15 years after last TCR1188-ABC cells administration","ALL","18 Years",false,{"inclusion":88,"exclusion":89,"raw_text":90},[],[],"Inclusion Criteria:\n\n1. Patients ≥ 18 years of age\n2. Patients with one of the following diagnoses:\n\n   1. Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma\n   2. Histologically confirmed metastatic colorectal cancer\n   3. Histologically confirmed metastatic non-small cell lung cancer\n3. HLA-A\\*11:01 positive as confirmed by a CLIA certified laboratory.\n4. KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.\n5. Received prior treatment for their primary malignancy as follows:\n\n   1. Pancreatic Cancer\u002FCholangiocarcinoma Patients: At least one prior line of standard of care therapy for advanced stage disease. For pancreatic cancer patients, this must include a gemcitabine or fluorouracil (5 FU)-based regimen.\n   2. Colorectal Cancer Patients: At least three prior lines of standard of care therapy for advanced stage disease. Prior treatment must include all of the following unless the patient was ineligible for a specific therapy type: i). a fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimen, ii). an anti-vascular endothelial growth factor (VEGF) agent, and iii). regorafenib, trifluridine-tipiracil, or fruquintinib. Patients with microsatellite instability-high (MSI-H) disease must also have received, or be ineligible for, prior treatment with an immune checkpoint inhibitor.\n   3. Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.\n6. Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.\n7. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:\n\n   1. Serum creatinine ≤ 1.5 mg\u002Fdl or creatinine clearance ≥ 50 cc\u002Fmin per the Cockcroft-Gault Equation; Patient must not be on dialysis.\n   2. ALT\u002FAST ≤ 5 x ULN (patients with liver metastases) or ALT\u002FAST ≤ 2.5 x ULN (patients without liver metastases)\n   3. Total bilirubin ≤ 1.5 mg\u002FdL x ULN, unless the subject has Gilbert's syndrome (if so, direct bilirubin must be ≤ 2.0 mg\u002FdL x ULN)\n   4. Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO\u002FMUGA\n   5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \\> 92% on room air\n8. Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:\n\n   1. Hemoglobin ≥ 8 g\u002FdL\n   2. Absolute neutrophil count ≥ 1000\u002FμL\n   3. Platelet count ≥ 100,000\u002FμL\n9. ECOG Performance Status that is either 0 or 1.\n10. Signed, written informed consent\n\nExclusion Criteria:\n\n1. Active hepatitis B or hepatitis C infection\n2. Patients with a severe acquired or inherited immunodeficiency, including HIV positive patients with a CD4 count ≤ 350 cells\u002FμL. In order to qualify, HIV positive patients must also be on an established antiretroviral therapy regimen with a viral load of \\\u003C400 copies\u002FmL.\n3. Any other active, uncontrolled infection.\n4. Class III\u002FIV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5).\n5. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.\n6. Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \\[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\\].\n7. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.\n8. Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg\u002Fday or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.6.\n9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.\n10. Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and\u002For myocardial infarction within 6 months of physician-investigator confirmation of eligibility.\n11. Prior history of myocarditis.\n12. Patients with pneumonitis\u002Finterstitial lung disease requiring steroid treatment.\n13. Patients with active\u002Funtreated brain metastases. \\[Note: History of treated metastases may still be eligible.\\]\n14. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.",[92,93],"ADULT","OLDER_ADULT",[95],{"facility":12,"status":8,"city":96,"state":97,"zip":98,"country":99,"contacts":100,"geoPoint":106},"Philadelphia","Pennsylvania","19104","United States",[101],{"name":102,"role":103,"phone":104,"email":105},"Abramson Cancer Center Clinical Trials Service","CONTACT","215-349-8245","PMCancerResearch@pennmedicine.upenn.edu",{"lat":107,"lon":108},39.95238,-75.16362,[110],{"name":102,"role":103,"phone":104,"email":105},[],[],[],{"nct_id":4,"conditions":115,"biomarkers":118},[18,116,117,21],"Colorectal Carcinoma","Lung Non-Small Cell Carcinoma",[119,120],"GTPase KRas","HLA-A Gene",{"nct_id":4,"found":14,"summary":122,"prompt_version":132},{"design":123,"status":124,"heading":125,"summary":126,"follow_up":127,"word_count":128,"commitments":129,"compensation":130,"drugs_mentioned":131},"This is a Phase I, open-label study, meaning both you and the study team will know what treatment you are receiving. It aims to enroll 30 participants to find the right dose.","completed","TCR1188-ABC Cells for KRAS-mutated Cancers","This study is testing a new cell therapy called TCR1188-ABC cells for people with certain advanced cancers that have a specific genetic change called a KRAS mutation. These cancers include pancreatic, colorectal, non-small cell lung cancer, and cholangiocarcinoma (bile duct cancer). You would receive a single infusion of TCR1188-ABC cells, along with other medications like Fludarabine, Cyclophosphamide, and Tocilizumab. The main goals are to see how safe the treatment is, if it can be successfully made for each patient, and to find the best dose. Researchers will watch for side effects for up to 15 years. You must be at least 18 years old and have a specific genetic marker called HLA-A*11:01.","Researchers will monitor you for treatment-related side effects for up to 15 years after receiving the TCR1188-ABC cells.",112,"Not specified in the trial record.","Not stated in the trial record.",[33,46],"v2"]