[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"endometrioid-ovarian-cancer\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:endometrioid-ovarian-cancer":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,42,93,118],{"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":24,"conditions":25,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100581914","phase-1-cirtuvivintolaparib-in-breast-cancer-susceptibility-genehomologous-recombination-deficiency-platinum-resistant-ovarian-cancer-100581914",false,"NCT06856499","Cirtuvivint\u002FOlaparib in Breast Cancer Susceptibility Gene\u002FHomologous Recombination Deficiency Platinum Resistant Ovarian Cancer","Phase I Evaluation of Combination CLK\u002FDYRK (Cirtuvivint) Inhibition With PARP Inhibition (Olaparib) in BRCA\u002FHRD Platinum Resistant Ovarian Cancer","Inclusion Criteria:\n\n1. Provision to sign and date the consent form.\n2. Stated willingness to comply with all study procedures and be available for the duration of the study.\n3. Woman aged ≥18 years of age\n4. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 1 or 2\n5. Patients must have a confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer\n6. Patients must have platinum-resistant disease defined as radiographic progression less than 6 months from last dose of most recent platinum therapy\n7. Patients must have measurable disease by defined RECIST 1.1 criteria\n8. Prior anticancer therapy:\n\n   * Patients must have received at least one prior platinum-based chemotherapy regimen\n   * Patients may not have received more than 3 prior lines of systemic therapy\n   * Neoadjuvant +\u002F- adjuvant therapies are considered 1 line of therapy\n   * Maintenance therapy (eg, Bevacizumab, PARP inhibitors) will be considered part of preceding line of therapy (ie, not counted independently)\n   * Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)\n   * Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance\n   * Prior radiation is allowed and is not considered a line of treatment\n9. Patients must have had testing for BRCA mutation (tumor or germline) and tumor HRD testing, and have been positive for one and\u002For the other.\n10. Patients must have received a prior PARP inhibitor as either treatment or maintenance therapy\n11. Patients must have adequate hematologic, liver, and kidney function as defined as:\n\n    * Absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL (1500\u002FµL)\n    * Platelet count ≥ 100 x 109\u002FL (100,000 µL)\n    * Hemoglobin ≥ 10.0 g\u002FdL with no blood transfusion in the past 28 days\n    * Serum creatinine ≤ 1.5 x upper limit of normal (ULN)\n    * Patients must have creatinine clearance estimated of ≥51 mL\u002Fmin using the Cockcroft-Gault equation or based on a 24 hour urine test\n    * Aspartate aminotransferase (AST)(Serum Glutamic Oxaloacetic Transaminase (SGOT)) and alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN unless liver metastases are present in which case they must be ≤ 5x ULN\n    * Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \\\u003C 3.0 x ULN)\n    * Serum albumin ≥ 2 g\u002FdL\n12. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n13. Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible.\n\nExclusion Criteria:\n\n1. Patients with clear cell, mucinous, sarcomatous, low grade\u002Fborderline, germ cell, or sex-cord stromal type ovarian tumor\n2. Patients with platinum refractory disease as defined by those who have progressed during or within 4 weeks of receiving platinum-based therapy\n3. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment\n4. Patients with myelodysplastic syndrome\u002Facute myeloid leukemia or with features suggestive of myelodysplastic syndrome\u002Facute myeloid leukemia.\n5. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to:\n\n   * Uncontrolled major seizure disorder\n   * Unstable spinal cord compression\n   * Any psychiatric disorder that prohibits obtaining informed consent.\n   * Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of therapy\n6. Patients with clinically significant cardiac disease including, but not limited to, any of the following\n\n   * Myocardial infarction ≤ 6 months prior to first dose\n   * Uncontrolled ventricular arrhythmia, recent (within 3 months)\n   * Superior vena cava syndrome\n   * Unstable angina pectoris\n   * Uncontrolled congestive heart failure (New York Heart Association \\> class II)\n   * Uncontrolled ≥ Grade 3 hypertension (per CTCAE)\n   * Uncontrolled cardiac arrhythmias\n7. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment\n8. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)\n9. Persistent toxicities (\\>\u002F= Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia or peripheral sensory neuropathy\n10. Patients with duodenal stent or other GI disorder\u002Fdefect that would interfere with absorption of oral medication\n\n    o Includes patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication\n11. Patients with known untreated or symptomatic central nervous system (CNS) metastases\n12. Prior known hypersensitivity reaction to study drugs and\u002For any of their excipients\n13. Minor or major surgical procedure within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.\n14. Inability to comply with study and follow-up procedures\n15. Patients deemed otherwise clinically unfit for clinical trial per investigators discretion.","FEMALE","18 Years",{"count":19,"type":20},50,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer. The study also aims to determine the recommended dose of the combination therapy.\n\nIf a participant is a good fit for the study, and they enroll in the study, they will:\n\n* Visit the clinic often at the beginning of the study for physical exams, blood draws, vital signs, and other study and routine care procedures. After the first two months participants will visit the clinic every 28 days.\n* Take the study medications, Cirtuvivint and Olaparib. Participants will take Olaparib every day. Participants will either take Cirtuvivint 5 days per week or 2 days per week.",[26,27,28],"Endometrioid Ovarian Cancer","Primary Peritoneal Cancer","Fallopian Tube Cancer","RECRUITING","2026-06-02",{"date":32,"type":33},"2026-06-04","ACTUAL",{"date":35,"type":33},"2025-12-08",{"date":37,"type":20},"2029-07",{"name":39,"class":40},"University of Colorado, Denver","OTHER",2,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":49,"targetDuration":4,"studyType":21,"phases":51,"briefSummary":53,"conditions":54,"keywords":59,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":82,"lastUpdatePostDateStruct":83,"startDateStruct":85,"completionDateStruct":87,"leadSponsor":89,"locationsCount":92},"100460887","phase-3-efficacy--safety-of-olvi-vec-and-platinum-doublet--bevacizumab-compared-to-physicians-choice-of-chemotherapy-and-bevacizumab-in-platinum-resistantrefractory-ovarian-cancer-prroc-onprime-gog-3076-100460887","NCT05281471","Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant\u002FRefractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)","A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Physician's Choice of Chemotherapy and Bevacizumab in Women With Platinum-Resistant\u002FRefractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)","Inclusion Criteria:\n\n* Histologically confirmed (from prior treatment) non-resectable ovarian, fallopian tube or primary peritoneal cancer.\n* High-grade serous \\[including malignant mixed Mullerian tumor (MMMT) with metastasis that contains high-grade epithelial carcinoma, FIGO grades 2 \\& 3 allowed\\], endometrioid, or clear-cell ovarian cancer.\n* Performance status ECOG of 0 or 1.\n* Life expectancy of at least 6 months.\n* Received a minimum of 3 prior lines (including the 1st line) of systemic therapy with no maximal limit.\n* Platinum-resistant or -refractory disease based on platinum-free interval (PFI) from the last dose of the most recent. platinum-based line of therapy (must have received a minimum of 2 doses of platinum in that line) to subsequent disease progression based on radiological assessment. Platinum-refractory: PFI of \\\u003C 1 month (including disease progression while on platinum-based therapy). Platinum-resistant: PFI of 1-6 months.\n* Received prior bevacizumab (or biosimilar) treatment.\n* No contraindication to receive carboplatin, cisplatin or bevacizumab (or biosimilar).\n* Have disease progression after last prior line of therapy based on radiological assessment prior to randomization.\n* At least 1 measurable target lesion per RECIST 1.1 based on abdominal\u002Fpelvis imaging scan at screening.\n* Evidence by CT and\u002For PET scans or physical exam of abdominal\u002Fpelvis region likely having disease in the peritoneal cavity (i.e., peritoneal carcinomatosis).\n* Adequate renal, hepatic, bone marrow function, adequate coagulation tests, adequate immune function by lymphocyte count.\n\nExclusion Criteria:\n\n* Tumors of mucinous, low-grade serous, squamous cell, small cell neuroendocrine subtypes, MMMT tumors absent an epithelial component on recent biopsy, or non-epithelial ovarian cancers (e.g., germ cell tumors, Sex-cord tumors).\n* Bowel obstruction within last 3 months prior to screening.\n* Active urinary tract infection, pneumonia, other systemic infections.\n* Active gastrointestinal bleeding.\n* Known current central nervous system (CNS) metastasis.\n* Inflammatory diseases of the bowel.\n* History of HIV infection.\n* Active hepatitis B virus or hepatitis C virus within 4 weeks prior to study.\n* History of thromboembolic event within the prior 3 months.\n* Contraindications for intraperitoneal (IP) catheter placement: Bowel obstruction with distended abdomen, rigid abdomen with bulky anterior wall carcinomatosis, abdominal wall hernia mesh that precludes laparoscopic entry to abdomen.\n* Clinically significant cardiac disease at screening (New York Heart Association Class III\u002FIV).\n* Acute cerebrovascular event(s) such as cerebrovascular accident (CVA) or transient ischemic attack (TIA) in previous 6 months.\n* Oxygen saturation \\\u003C90%.\n* Received prior virus-based gene therapy or therapy with cytolytic virus of any type.\n* Receiving concurrent antiviral agent.\n* Prior malignancy of other histology active within previous 3 years except for locally curable cancers apparently cured such as basal\u002Fsquamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, any other stage I\u002FII local malignancies.\n* Received chemotherapy, radiotherapy, other anti-cancer biologic therapies within 4 weeks prior to planned treatment.\n* Underwent surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to first study treatment in either Arm.\n* Receiving immunosuppressive therapy or steroids (except acute concurrent corticosteroid of no more than 20 mg per day for medical management with prednisolone equivalent.\n* Symptomatic malignant ascites or pleural effusions defined as rapidly progressive ascites with abdominal distension and gastrointestinal dysfunction, pleural effusions with respiratory difficulties requiring frequent paracentesis \\> once every 14 days.\n* Known hypersensitivity to gentamicin.",{"count":50,"type":20},186,[52],"PHASE3","The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant\u002Frefractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant\u002Frefractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.",[55,56,28,27,57,26,58],"Platinum-resistant Ovarian Cancer","Platinum-refractory Ovarian Cancer","High-grade Serous Ovarian Cancer","Ovarian Clear Cell Carcinoma",[60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81],"olvimulogene nanivacirepvec","GL-ONC1","GLV-1h68","oncolytic virus","virotherapy","viral therapy","immunotherapy","immunochemotherapy","combination therapy","vaccinia virus","ovarian cancer","fallopian tube cancer","primary peritoneal cancer","platinum resistant","platinum refractory","recurrent ovarian cancer","platinum resensitization","chemoresistance","heavily pre-treated","immune activation","reversal of platinum resistance or refractoriness","resensitize","2026-03-16",{"date":84,"type":33},"2026-03-18",{"date":86,"type":33},"2022-08-31",{"date":88,"type":20},"2026-10",{"name":90,"class":91},"Genelux Corporation","INDUSTRY",31,{"id":94,"slug":95,"hasResults":11,"nctId":96,"briefTitle":97,"officialTitle":98,"acronym":4,"eligibilityCriteria":99,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":100,"targetDuration":4,"studyType":21,"phases":102,"briefSummary":104,"conditions":105,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":108,"lastUpdatePostDateStruct":109,"startDateStruct":111,"completionDateStruct":113,"leadSponsor":115,"locationsCount":117},"100569171","phase-2-catalina-2-a-clinical-study-of-torl-1-23-in-platinum-resistant-ovarian-cancer-100569171","NCT06690775","CATALINA-2: A Clinical Study of TORL-1-23 in Platinum-resistant Ovarian Cancer.","Catalina-2: A Phase 2 Study Evaluating the Efficacy and Safety of TORL-1-23 in Women With Advanced Platinum-Resistant Epithelial Ovarian Cancer (Including Primary Peritoneal and Fallopian Tube Cancers) Expressing Claudin 6","Inclusion Criteria:\n\nParticipants are eligible to be included in the study only if all the following criteria apply:\n\n1. Females ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent.\n2. Participants must sign the informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n3. Disease Type:\n\n   * Histologically or cytologically confirmed diagnosis of advanced (unresectable) or metastatic high grade serous ovarian, primary peritoneal (i.e, of primary origin), or fallopian tube cancer. High-grade endometrioid ovarian cancer is permitted for enrollment.\n   * Participant's tumor must be positive for CLDN6 expression as defined by the CLDN6 reference laboratory assay. Tumor tissue will be required for submission for CLDN6 testing prior to Cycle 1 Day 1.\n   * Participants must have platinum-resistant disease, defined as the following:\n   * If participants received only 1 line of platinum-based therapy, they must have completed 4 or more cycles of platinum-containing therapy, must have achieved a CR or PR, and progressed \\>3 months but ≤6 months after the last dose of platinum.\n   * Participants who have received more than 1 line of platinum- based therapy must have progressed on or within 6 months after the last dose of platinum.\n   * NOTE: This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression (per RECIST v1.1).\n   * Participants who are platinum-refractory during front-line treatment are excluded.\n   * Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single- agent therapy is appropriate as the next line of treatment. Study rules for evaluation of number of prior systemic lines of therapy:\n   * Adjuvant ± neoadjuvant is considered one line of therapy\n   * Maintenance therapy (eg, bevacizumab or PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently)\n   * Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)\n   * Hormonal therapy will not be counted as a separate line of therapy\n4. Measurable disease, per RECIST v1.1\n5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.\n6. Adequate organ function, based on the following laboratory values:\n\n   * ANC: ≥1,500\u002FmcL\n   * Platelets: ≥100,000\u002FmcL without transfusion within 4 weeks of first dose\n   * Hemoglobin: 9 g\u002FdL with transfusion or EPO support up to 14 days before eligibility assessment\n   * Measured or calculated creatinine clearance with a validated formula\\*: ≥30 mL\u002Fmin\n   * Serum total bilirubin: ≤1.5 X ULN (participants with known Gilbert disease or liver metastases who have serum bilirubin level ≤3×ULN may be enrolled\n   * AST (SGOT) and ALT (SGPT): ≤3 X ULN (participants with active liver metastases who have ALT\u002FAST ≤5 X ULN may be enrolled)\n   * Albumin: ≥2.5 g\u002FdL\n   * ECG: 12-Lead ECG with normal tracing or non-clinically significant changes that do not require medical intervention and QTcF interval\n\n     * 470 msec and without history of Torsades des Pointes or other symptomatic QTc abnormality.\n7. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours before starting study drug treatment. The serum pregnancy test must be negative for the participant to be eligible.\n8. Participants must agree to use a highly effective birth control method from the time of the first study drug treatment through 7 months after the last study drug treatment, or be of nonchildbearing potential.\n9. Participants must agree not to donate eggs from the first study drug treatment through 7 months after the last study drug treatment.\n10. Participants must agree to not breastfeed from the first dose of study treatment through 90 days after the last dose of study treatment.\n\nExclusion Criteria:\n\nParticipants are excluded from the study if any of the following criteria apply:\n\n1. Has not recovered \\[recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, Grade ≤1\\] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.\n2. Participants with clear cell, mucinous, sarcomatous (including carcinosarcoma), mixed histology, or low-grade, borderline ovarian tumors or non-epithelial ovarian cancers.\n3. Participants with primary platinum-refractory ovarian, primary peritoneal (i.e. of primary origin) or fallopian tube cancer, defined as disease that did not respond to or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy.\n4. Received prior chemotherapeutic, investigational, radiotherapy, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-1-23. There is no waiting period required for stereotactic radiosurgery.\n5. Prior treatment with a CLDN6-targeting agent or an MMAE-containing ADC.\n6. Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded.\n7. Grade 2 or greater peripheral neuropathy.\n8. History of non-infectious pneumonitis\u002FILD within 6 months of first dose of study drug.\n9. Participants must not be considered a high medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.\n10. History of significant cardiac disease:\n\n    1. Congestive heart failure \\>New York Heart Association class 2 within last year\n    2. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)\n    3. Myocardial infarction less than 6 months before start of study drug\n    4. Anti-arrhythmic therapy (beta blockers are permitted)\n    5. Any unstable ischemic disease or untreated arrhythmia\n11. Known history of myelodysplastic syndrome or acute myeloid leukemia.\n12. History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. Participants with malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ of the breast are not excluded.\n13. Uncontrolled infection; active, clinically serious infections (CTCAE Grade \\>2).\n14. Participants with seizure disorder requiring medication.\n15. Known hypersensitivity or intolerance to any of the study drugs, study drug classes, or excipients in the formulation.\n16. History of having an allogeneic bone marrow or organ transplant.\n17. Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator.\n18. Participants who are taking any drugs that are strong inducers and\u002For strong inhibitors of CYP3A4 enzymes.\n19. Participants who are taking any drugs that are inhibitors of P-glycoprotein.",{"count":101,"type":20},230,[103],"PHASE2","A Phase 2 study to evaluate the safety and efficacy of TORL-1-23 in patients with advanced ovarian cancer.",[106,107,28,26],"Epithelial Ovarian Cancer","Primary Peritoneal","2025-12-19",{"date":110,"type":33},"2025-12-23",{"date":112,"type":33},"2024-11-20",{"date":114,"type":20},"2027-12",{"name":116,"class":91},"TORL Biotherapeutics, LLC",66,{"id":119,"slug":120,"hasResults":11,"nctId":121,"briefTitle":122,"officialTitle":123,"acronym":4,"eligibilityCriteria":124,"healthyVolunteers":11,"sex":125,"minAge":17,"maxAge":4,"enrollmentInfo":126,"targetDuration":4,"studyType":21,"phases":128,"briefSummary":129,"conditions":130,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":139,"leadSponsor":141,"locationsCount":143},"100470262","phase-1-a-study-of-ni-1801-in-patients-with-mesothelin-expressing-solid-cancers-100470262","NCT05403554","A Study of NI-1801 in Patients with Mesothelin Expressing Solid Cancers","A Phase 1, Open-Label, Dose Finding Study of NI-1801, a Bispecific Mesothelin X CD47 Engaging Antibody, As a Single Agent, in Combination with Anti-PD-1 Antibody, and in Combination with Weekly Paclitaxel (Standard of Care) in Patients with Mesothelin Expressing Ovarian, Pancreatic, Non-Small-Cell-Lung and Triple-Negative Breast Cancers","Main Inclusion Criteria for the Single Agent Dose Escalation and the Combination with Pembrolizumab:\n\n1. Adults ≥ 18 years of age at the time of signing the informed consent form\n2. Histologically or cytologically confirmed diagnosis of epithelial OC (high-grade serous or endometroid), TNBC, or non-squamous NSCLC. For the combination with pembrolizumab, only subjects with histologically or cytologically confirmed diagnosis of epithelial OC (high-grade serous or endometroid), non-squamous NSCLC and ductal pancreatic adenocarcinoma.\n3. MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 40% of tumor cells. Staining for MSLN expression can be performed using archival tumor tissue and is foreseen to be performed at the institution's pathology. A slice for centralized IHC assessment for validation and biomarker analysis is mandatory.\n4. Patients with advanced, metastatic, or recurrent disease\n\n   * after at least 1 prior systemic treatment for the primary malignancy and\n   * who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer a clinical benefit to patients with these tumor entities.\n5. Measurable disease according to the revised RECIST guideline version 1.1(3)\n6. Patients treated in either the single agent recommended dose expansion cohort or in the combination with pembrolizumab cohort should have accessible lesions at screening for baseline and on treatment biopsies.\n7. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.\n8. Negative pregnancy test at inclusion.\n9. Life expectancy of at least 2 months.\n\nMain Inclusion Criteria for the Randomized study arm:\n\n1. Female patients ≥ 18 years of age.\n2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer.\n3. Patients must have platinum-resistant disease:\n\n   3.1. Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between greater than 3 months and ≤ 6 months after the date of the last dose of platinum.\n\n   3.2. Patients who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum\n4. Patients must have progressed radiographically on or after their most recent line of therapy.\n5. Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low risk, medically routine procedure for IHC confirmation of MSLN expression.\n6. MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 40% of tumor cells. Staining for MSLN expression can be performed using archival tumor tissue and can be done at the institution's pathology. A slice for centralized IHC assessment for validation and biomarker analysis is mandatory.\n7. Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator).\n8. Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment:\n\n   * Adjuvant ± neoadjuvant considered one line of therapy\n   * Maintenance therapy (e.g., bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (i.e., not counted independently)\n   * Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (i.e., not counted independently)\n   * Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance\n9. ECOG PS of 0 or 1\n10. Time from prior therapy:\n\n    * Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)\n    * Focal radiation completed at least 2 weeks prior to first dose of study drug\n11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities.\n12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery.\n13. Patients must have adequate hematologic, liver and kidney functions\n14. Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.\n15. Negative pregnancy test at inclusion\n\nMain Exclusion Criteria for the Single Agent Dose Escalation and the Combination with Pembrolizumab:\n\n1. Patient has known hypersensitivity to NI-1801 or any of the constituent compounds.\n2. Radiotherapy to the target lesions within 4 weeks prior to the first NI-1801 infusion.\n3. Prior anti-cancer therapy including chemotherapy, hormonal therapy, and investigational agents within 2 weeks or within ≤ 5 half-lives prior to starting NI-1801 dosing (up to a maximum of 4 weeks), whichever is longer. The maximum required washout period will thus not exceed 4 weeks prior to the day of first treatment with NI-1801. Note: Low dose steroids (oral prednisone or equivalent ≤ 20 mg per day, including systemic or topic use), localized noncentral nervous system (CNS) radiotherapy of non-target lesions, and treatment with bisphosphonates and RANKL inhibitors are not criteria for exclusion.\n4. Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study. COVID-19 vaccination is allowed only starting from Cycle 2 (if not completed before study inclusion).\n5. Severe cardiac dysfunction (NYHA classification III-IV).\n6. Significant hepatic dysfunction (serum bilirubin ≥ 1.5 mg\u002FdL or AST and\u002For ALT ≥ 2.5 times normal level), unless related to liver metastasis.\n7. Patients with known human immunodeficiency virus (HIV) infection or known history or serological evidence of prior hepatitis B or C virus infection. Active SARS-COV2 infection.\n8. Uncontrolled active systemic bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs\u002Fsymptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks prior to first dose of NI-1801.\n9. Patients with concomitant active malignancy, requiring ongoing systemic treatment.\n10. Patients with known CNS metastases.\n11. Platelet count lower than 100 x 10\\^9\u002FL (transfusion support within 14 days before the test is not allowed).\n12. Hemoglobin lower than 10.0 g\u002FdL. Prior RBC transfusion is permitted.\n13. ANC lower than 1 x 10\\^9\u002FL (the use of colony stimulating factors, G-CSF or GM-CSF, within 14 days before the test is not allowed).\n14. Pregnancy and lactation.\n15. History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements or give informed consent.\n16. Significant medical diseases or conditions, including laboratory abnormalities, as assessed by the Investigators and Sponsor, which would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, and severely immunocompromised state, major surgery ≤ 4 weeks prior to starting NI-1801.\n17. Prior treatment with a CD47, SIRPα, or MSLN targeting agent.\n18. Patients in whom acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure have not resolved to Grade ≤ 1 or returned to baseline except for alopecia (any grade), anemia, and peripheral neuropathy (for the latter, recovery to Grade ≤ 2 is acceptable).\n19. People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship\u002Fcuratorship), people who are unable to express their consent, and people who are subject to a legal guardianship order.\n\nFurthermore, subjects presenting with any of the following criteria will not be included in the sub-study (combination with pembrolizumab cohort):\n\n* History of\u002Factive non-infectious pneumonitis or interstitial lung disease.\n* Known hypersensitivity to pembrolizumab or excipients.\n* Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n* Prior organ or tissue allograft.\n* History of Grade ≥ 3 toxicity related to prior T-cell agonist or checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures.\n* History of myocarditis, regardless of etiology.\n\nMain Exclusion Criteria for the Randomized study arm:\n\n1. Patients with clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histology, or low-grade or borderline ovarian tumor.\n2. Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy.\n3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow.\n4. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:\n\n   * Active hepatitis B or C infection (whether or not on active antiviral therapy)\n   * HIV infection\n   * Active cytomegalovirus infection\n   * Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated\n   * Patients with history of multiple sclerosis or other demyelinating disease and\u002For Lambert-Eaton syndrome (paraneoplastic syndrome)\n5. Patients with clinically significant cardiac disease including, but not limited to, any one of the following:\n\n   * Myocardial infarction ≤ 6 months prior to first dose\n   * Unstable angina pectoris\n   * Uncontrolled congestive heart failure (New York Heart Association greater than class II)\n   * Uncontrolled ≥ Grade 3 hypertension (per CTCAE)\n   * Uncontrolled cardiac arrhythmias\n   * Patients assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan\n   * History of hemorrhagic or ischemic stroke within six months prior to randomization\n6. History of cirrhotic liver disease (Child-Pugh Class B or C)\n7. Previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis\n8. Patients with prior hypersensitivity to monoclonal antibodies.\n9. Women who are pregnant or lactating.\n10. Patients with prior treatment with a CD47, signal regulatory protein (SIRP) alpha, or MSLN targeting agent.\n11. Patients with central nervous system (CNS) metastases.\n12. Patients with a history of other malignancy within 3 years prior to randomization.\n13. Prior known hypersensitivity reactions to study drugs and\u002For any of their excipients.","ALL",{"count":127,"type":20},70,[23],"Study LCB-1801-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of NI-1801 in patients with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN).\n\nThe dose escalation part (Part A) of the main study will evaluate the safety and tolerability of escalating doses of NI-1801 to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of NI-1801. The expansion part (Part B) of the main study will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 10 additional subjects in order to determine the recommended Phase 2 dose (RP2D).\n\nTreatments will be administered in 28-day cycles for up to 12 months until disease progression, unacceptable toxicity, or Investigator\u002Fpatient decision to withdraw study consent.\n\nThe dose escalation part (Part A) of the sub-study will evaluate the safety and tolerability of escalating doses of NI-1801 in combination with anti-PD-1 antibody. The expansion part (Part B) of the sub-study will further evaluate the safety and efficacy of NI-1801 administered in combination with anti-PD-1 antibody at or below the MTD.\n\nIn the randomized cohort, the experimental arm will receive the investigational drug NI-1801 at the P2RD every two weeks in combination with weekly administration of paclitaxel (80 mg\u002Fm\\^2) over 4-week cycles. The control arm will be treated with weekly paclitaxel at the same regimen representing one of the standards of care (SoC) in this population. This trial specifically targets patients with platinum-resistant ovarian cancer. This cohort will be made up of 20 evaluable patients, 10 per arm.",[106,131,132,133,26],"Triple Negative Breast Cancer","Non-squamous Non-small-cell Lung Cancer","Pancreatic Adenocarcinoma (ductal Adenocarcinoma)","2024-10-25",{"date":136,"type":33},"2024-10-29",{"date":138,"type":33},"2022-04-29",{"date":140,"type":20},"2026-09-30",{"name":142,"class":91},"Light Chain Bioscience - Novimmune SA",7]