[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06451497":3,"trial-entities:NCT06451497":169,"trial-summary:NCT06451497":182},{"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":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":30,"study_type":31,"primary_purpose":32,"phases":33,"enrollment_info":35,"interventions":38,"primary_outcomes":47,"secondary_outcomes":66,"sex":99,"minimum_age":100,"maximum_age":17,"healthy_volunteers":101,"eligibility_criteria":102,"std_ages":106,"locations":109,"central_contacts":151,"overall_officials":160,"references":167,"see_also_links":168},"NCT06451497","ZM008-001","This is a Phase 1 Trial of ZM008, an Anti-LLT1 Antibody, Used as Single Agent Followed by Combination Treatment With Toripalimab in Patients With Advanced Solid Tumors","Phase 1 Dose Escalation Trial of ZM008, an Anti-LLT1 Antibody, as Single Agent Followed by Combination With Toripalimab in Patients With Advanced Solid Tumors","RECRUITING","2027-04","2026-03","2026-04-02","2024-05-22","Zumutor Biologics Inc.","INDUSTRY",true,"This is a phase 1 dose escalation trial of ZM008, an anti-LLT1 antibody as a single agent followed by combination with Toripalimab in patients with advanced solid tumors who have exhausted all standard therapy available or are intolerant of the same.",null,[19,20,21,22,23,24,25,26,27,28,29],"Non Small Cell Lung Cancer","Head and Neck Squamous Cell Carcinoma","Pancreas Adenocarcinoma","Biliary Tract Cancer","Prostate Cancer","Urothelial Carcinoma","Colorectal Cancer","Triple Negative Breast Cancer","High Grade Ovarian Serous Adenocarcinoma","Diffuse Large B Cell Lymphoma","Renal Cell Cancer Metastatic",[],"INTERVENTIONAL","OTHER",[34],"PHASE1",{"count":36,"type":37},100,"ESTIMATED",[39],{"type":40,"name":41,"description":42,"armGroupLabels":43,"otherNames":45},"BIOLOGICAL","ZM008","Intravenous delivery",[44],"Single arm dosing with ZM008 and in combination with Toripalimab",[46],"Antibody",[48,52,56,60,63],{"measure":49,"description":50,"timeFrame":51},"Nature and frequency of dose limiting toxicities per Common Toxicity Criteria for Adverse Events version 5","Adverse Events to be assessed.","This starts at the beginning of screening procedures and upto 90 days after completion of the last cycle of investigational product administration with each cycle of 21 days duration.",{"measure":53,"description":54,"timeFrame":55},"Change in systolic and diastolic BP,","Systolic \\& Diastolic measurements will be in mmHg","During screening (baseline), through the administration of investigational product (Day1 of each treatment cycle which is 21 days), end of treatment visit which is 30 days after completion of the last treatment cycle.",{"measure":57,"description":58,"timeFrame":59},"Change in Heart Rate","This will be measured in beats per minute.","During screening (baseline), through the administration of investigational product, (Day1 of each treatment cycle of 21 days duration), end of treatment visit at 30 days after completion of last cycle of investigational product.]",{"measure":61,"description":62,"timeFrame":59},"Changes in Temperature measurements.","This will be measured in degrees Fahrenheit",{"measure":64,"description":65,"timeFrame":51},"Change in pulse ox measurements on room air","Measurement of peripheral oxygen saturation as a percentage",[67,71,74,78,82,85,88,92,96],{"measure":68,"description":69,"timeFrame":70},"Overall Response Rate (ORR) per RECIST 1.1","This calculation is defined as the percentage of patients with partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 version 5 based on local investigator assessment.","Assessed at study completion in upto 36 months.",{"measure":72,"description":73,"timeFrame":70},"Immune Overall Response Rate (iORR) per iRECIST","This calculation is defined as the percentage of patients with partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors i(RECIST).",{"measure":75,"description":76,"timeFrame":77},"Progression Free Survival","This is defined as the start of study treatment until disease progression per RECIST 1.1 or death from any cause for patients that have not started any other treatment for tumor reduction.","From the start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months",{"measure":79,"description":80,"timeFrame":81},"Immune Progression Free Survival","This is defined as the start of study treatment until disease progression per iRECIST or death from any cause for patients that have not started any other treatment for tumor reduction.","From start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months",{"measure":83,"description":84,"timeFrame":81},"Disease Control Rate","This is defined as the percentage of patients with Complete Response, Partial Response and Stable Disease per RECIST criteria 1.1",{"measure":86,"description":87,"timeFrame":77},"Immune Disease Control Rate","This is defined as the percentage of patients with Complete Response, Partial Response and Stable Disease per iRECIST criteria",{"measure":89,"description":90,"timeFrame":91},"Immunogenicity of ZM008","Blood will be drawn for antibodies against ZM008","Baseline, and before every cycle of investigational product administration (with each cycle being 21 days duration) and 30 days after last cycle completion.",{"measure":93,"description":94,"timeFrame":95},"Maximum Plasma Concentration of the biological product ZM008","Blood will be drawn for evaluating the maximum plasma concentration in micrograms\u002Fmilliliter","Baseline, on Cycle 1 Day1 (before and end of ZM008 infusion, 2 hour, 6 hour, 10 hour and 24 hour after infusion), day 2, day 8 & day15. Blood tests will be repeated for Cycle 2. Cycle 3 &4 onwards only Day 1 blood will be drawn. Cycle duration is 21 days",{"measure":97,"description":98,"timeFrame":95},"Area Under the Plasma Concentration Versus Time Curve (AUC) of the biological product ZM008","Blood will be drawn at periodic intervals and the measure expressed as microgram\u002Fmilliliter versus time in hours","ALL","18 Years",false,{"inclusion":103,"exclusion":104,"raw_text":105},[],[],"Inclusion Criteria:\n\n1. Adult patients aged 18 years and older, at the time of signing the informed consent form.\n2. Part 1: Patients with histologically confirmed diagnosis of advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors that have no standard therapeutic option with a proven clinical benefit or are intolerant to these therapies with the following selected tumor histologies: NSCLC, triple-negative breast cancer, head and neck squamous cell carcinoma, prostate cancer, colorectal cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, high grade serous ovarian cancer, diffuse large B cell lymphoma, kidney cancer, or urothelial cancer. This selection corresponds to tumor histologies known to express higher LLT1 levels. Other tumor histologies can be enrolled only if approved by the sponsor after discussion with the investigator. Tumors should be progressing or deserving another anticancer treatment in the opinion of the investigator. Part 2: The same patient population as Part 1 although it will be enriched or modified based on the observed antitumor activity observed in Part 1. In case the patient population is modified to include patients with standard therapeutic alternatives, a substantial amendment will be issued.\n3. Patients with tumors with actionable mutations should have progressed to all approved targeted therapies or have them contraindicated.\n4. The patient has measurable disease with RECIST 1. 1 on computed tomography (CT), positron emission tomography (PET)\u002FCT, or magnetic resonance imaging (MRI) scan. Imaging tests outside the screening period are valid if performed not more than 3 weeks before consent signature and otherwise fulfill protocol criteria. Patients with non-measurable disease may be allowed in Part 1 only with the explicit approval of the trial Medical Monitor.\n5. The patient has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Patients with renal cell carcinoma (RCC) to be allocated to a backfill cohort in Part 1 can have PS ≤2.\n6. The patient has adequate hematologic function as defined by:\n\n   1. Hemoglobin ≥9 g\u002FdL (whole or partial blood transfusions not allowed in the two previous weeks).\n   2. Absolute neutrophil count (ANC) ≥1.0 × 109\u002FL (growth factors like granulocyte colony-stimulating factor are not allowed in the two previous weeks).\n   3. Platelet count ≥75 × 109\u002FL (platelet transfusions are not allowed in the two previous weeks).\n7. The patient has adequate hepatic function as defined by:\n\n   1. Total bilirubin ≤1.5 times upper limit of normal (ULN).\n   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 times ULN, (if liver metastases are present, then ≤5.0 times ULN is allowed).\n   3. The patient has adequate renal function as defined by: estimated creatinine clearance (CrCL) using the Cockcroft- Gault formula ≥30 mL\u002Fminute.\n8. Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must consent to adhere to contraceptive requirements as detailed in the protocol from the day of the signature of the informed consent to at least 4 months after the last dose of trial treatment.\n9. Suitable venous access for safe drug administration and the trial-required drug concentration and pharmacodynamic sampling.\n10. Permission to access archival biopsy located at the treating site or elsewhere. Note: Archival tissue does not need to be checked before Cycle 1 Day 1. The most modern archival biopsy is requested. If no archival tissue is available, the patient can still be enrolled in the escalation phase but not in Part 2.\n11. Pretreatment fresh biopsy is highly encouraged in Part 1 dose escalation once BED has been achieved. In Part 2, fresh pre-treatment and on-treatment biopsies should be obtained unless biopsy is associated with significant risk or declined by the patient and per discussion with the sponsor medical monitor (or designee).\n\nExclusion criteria:\n\n1. Patients should have recovered from toxicity related to previous anticancer treatments (including surgery and radiation) to Grade 0\u002F1 or baseline (except alopecia and peripheral neuropathy). Patients with endocrinopathies should have the replacement treatment in stable dosing.\n2. The patient has a history of uncontrolled brain metastasis. Patients with brain metastases are allowed if they are previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery and have new brain imaging confirming that brain metastasis are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or CT) and considered controlled with \\\u003C10 mg\u002Fday prednisone equivalent at the time of receiving the first dose of ZM008. For asymptomatic patients, screening brain imaging is not required.\n3. The patient has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation for palliation), and who has not recovered to Grade ≤1 or baseline from related side effects of such therapy (except for alopecia).\n4. The patient had an active infection requiring parenteral or oral antibiotics at the time of the first dose. Patients receiving oral antibiotics can be enrolled after discussion and approval of the trial Medical Monitor.\n5. The patient has evidence of serious uncontrolled medical disorder that, in the opinion of the investigator or Medical Monitor, makes it unwise for the patient to participate in the trial or that might jeopardize compliance with the protocol.\n6. The patient has a psychiatric illness\u002Fsocial circumstance that would limit compliance with trial requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.\n7. The patient has clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting, in situ cervical cancer, in situ breast carcinoma or localized non-melanoma skin cancers.\n8. The patient has uncontrolled or significant cardiovascular disease defined as New York Heart Association classification III or IV.\n9. The patient has baseline QTc (using the Fridericia correction calculation) \\>470 msec in patients without pacemaker. Active autoimmune disease that is requiring systemic treatment (i.e., with use of disease modifying agents, corticosteroids at \\>10 mg\u002Fday of equivalent prednisone, or immunosuppressive drugs at any dose). 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. Participants with adrenal insufficiency on oral steroid replacement are allowed to participate in the study. Participants with controlled type I diabetes mellitus on stable insulin regimen are also eligible for the study. Participants with rheumatoid arthritis or psoriasis may be eligible if they have not experienced a flare in 2 years and do not require systemic therapy within the past year. Participants with vitiligo are also eligible.\n10. Use of therapeutic immunosuppressive medication (eg, prednisone dose of ≥ 10 mg\u002Fday or equivalent, tumor necrosis factor inhibitors at any dose) within 28 days prior to the first planned dose of study treatment. This does not include intranasal, intraocular, inhaled corticosteroids, topical and intra-articular joint injections, or physiologic replacement doses of systemic corticosteroids. Less than 10 mg prednisone per day or equivalent, short term, is allowed.\n11. For patients in the ZM008 monotherapy and combination arms: Patients who discontinued prior treatment with any immune checkpoint due to immune-related AEs, irrespective of grade, recovery, or need for continued steroid therapy. Also, patients without formal contraindication due to previous irAE are not eligible if the AE has not resolved to Grade 1 or better and\u002For still requires steroids (\\>10 mg of prednisone equivalent per day) for ongoing management.\n12. History of interstitial lung disease\u002Fnon-infectious pneumonitis, including immune-related pneumonitis of any Grade, radiation pneumonitis, active pulmonary tuberculosis, or evidence of active pneumonitis on screening chest CT scan. Participants with radiation therapy to the lung that is \\>30 Gy within 6 months of the first dose of treatment are excluded. Participants with active lung infections requiring treatment are also excluded.\n13. The patient has live vaccines reception within 30 days of enrollment.\n14. Known active hepatitis B or C.\n15. Patients positive for human immunodeficiency virus (HIV) can be enrolled only in Part 2 of the trial, but HIV-positive patients must meet the following criteria: a. have CD4+ T cell (CD4+) counts ≥350 cells\u002FμL. b. have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the trial. c. should be on established antiretroviral therapy for at least 4 weeks. d. have an HIV viral load of less than 400 copies\u002FmL prior to enrollment. e. known history of any other relevant congenital or acquired immunodeficiency other than HIV infection.\n16. Has known or suspected allergy to trial treatment, excipients, or related products.\n17. Prior allogeneic bone marrow transplantation or solid organ transplantation.\n18. Toripalimab cohort only: Any contraindication present in the toripalimab prescribing information.",[107,108],"ADULT","OLDER_ADULT",[110,126,140],{"facility":111,"status":8,"city":112,"state":113,"zip":114,"country":115,"contacts":116,"geoPoint":123},"Dana Farber Cancer Institute","Boston","Massachusetts","02215","United States",[117,121],{"name":118,"role":119,"phone":120},"Glenn Hanna, MD","CONTACT","617-632-6799",{"name":118,"role":122},"PRINCIPAL_INVESTIGATOR",{"lat":124,"lon":125},42.35843,-71.05977,{"facility":127,"status":8,"city":128,"state":129,"zip":130,"country":115,"contacts":131,"geoPoint":137},"NEXT Oncology","Austin, TX 78758","Texas","78758",[132,135],{"name":133,"role":119,"phone":134},"Andrae Vandross, MD","210-580-9500",{"name":136,"role":122},"Andrae Vandros, MD",{"lat":138,"lon":139},30.26715,-97.74306,{"facility":127,"status":8,"city":141,"state":129,"zip":142,"country":115,"contacts":143,"geoPoint":148},"San Antonio","78229",[144,146],{"name":145,"role":119,"phone":134},"Ildefonso Rivera, MD",{"name":147,"role":122},"Ildefonso IR Rivera, MD",{"lat":149,"lon":150},29.42412,-98.49363,[152,156],{"name":153,"role":119,"phone":154,"email":155},"Maloy Ghosh, PhD","+91 80 69121400","maloy.ghosh@zumutor.com",{"name":157,"role":119,"phone":158,"email":159},"Jyotsna Fuloria, MD","5046062594","jyotsna.fuloria@fuloriaresearch.org",[161,163],{"name":153,"affiliation":13,"role":162},"STUDY_CHAIR",{"name":164,"affiliation":165,"role":166},"Jyotsna Fuloria","Fuloria Clinical Research Solutions LLC","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":170,"biomarkers":181},[171,172,20,173,174,175,176,177,178,179,180,24],"Colorectal Carcinoma","Diffuse Large B-Cell Lymphoma","Lung Non-Small Cell Carcinoma","Malignant neoplasm of biliary tract","Ovarian High Grade Serous Adenocarcinoma","Pancreatic Ductal Adenocarcinoma","Prostate Carcinoma","Renal Cell Carcinoma","Solid Neoplasm","Triple-negative breast cancer",[],{"nct_id":4,"found":15,"summary":183,"prompt_version":193},{"design":184,"status":185,"heading":186,"summary":187,"follow_up":188,"word_count":189,"commitments":190,"compensation":191,"drugs_mentioned":192},"This is a Phase 1 study, meaning it's an early-stage trial to test safety and dosage. It plans to enroll 100 adult participants.","completed","Phase 1 ZM008 and Toripalimab for Advanced Solid Tumors","This study is testing a new treatment called ZM008, an antibody, first by itself and then in combination with another drug called Toripalimab. It's for people with advanced solid tumors, such as non-small cell lung cancer, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, biliary tract cancer, or prostate cancer, who have already tried standard treatments or can't tolerate them. The main goal is to see how safe the treatment is and what side effects it might cause, especially looking at dose-limiting toxicities (serious side effects that might require reducing the dose). Researchers will also monitor your blood pressure and heart rate. You can join if you are 18 or older and have one of the specified advanced solid tumors.","You will be followed for safety up to 90 days after completing your last treatment cycle, and for blood pressure and heart rate changes 30 days after your last treatment.",120,"You would receive ZM008 intravenously (through a vein). Treatment cycles are 21 days long. Your blood pressure and heart rate will be checked during screening, on Day 1 of each treatment cycle, and at a follow-up visit 30 days after your last treatment.","Not stated in the trial record.",[41],"v2"]