[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Anwaar Saeed\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":101},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,44,75],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100584963","phase-1-9-ing-41-combined-with-retifanlimab-plus-modified-folfirinox-for-patients-with-advanced-pancreatic-adenocarcinoma-riley-100584963",false,"NCT06896188","9-ING-41 Combined With Retifanlimab, Plus Modified FOLFIRINOX for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)","A Phase Ib Study of 9-ING-41 (Elraglusib), a Glycogen Synthase Kinase 3-beta (GSK-3β) Inhibitor, Combined With Retifanlimab, a PD-1 Inhibitor, Plus Modified FOLFIRINOX as Frontline Therapy for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)","RiLEY","Inclusion Criteria:\n\n* Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.\n* Is aged ≥ 18 years.\n* Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced\u002Fmetastatic setting.\n* Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post radiation on a subsequent scan prior to trial enrollment.\n* Must have available archived FFPE tumor tissue at study entry; FFPE tissue block preferred or 10 unstained slides (metastatic tissue preferred to primary tissue) OR if FFPE archived tissue is not available, willing to provide a standard fresh tumor biopsy prior to start of study treatment for molecular profiling of the tumor using standard institutional oncomine panel. If oncomine testing has previously been completed, a repeat biopsy or testing is not required.\n* Has laboratory function within specified parameters (may be repeated):\n* Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1,500\u002FmL; hemoglobin ≥ 8.5 g\u002FdL, platelets ≥ 100,000\u002FmL\n* Adequate liver function: transaminases (aspartate aminotransferase\u002F alanine aminotransferase, AST\u002FALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN\n* Adequate renal function: CrCl \\> 60 mL\u002Fmin measured or calculated by Cockcroft-Gault (C-G) equation (estimated glomerular filtration rate \\[eGFR\\] can also be used in place of CrCl)\n* Serum amylase and lipase ≤ 1.5 x ULN\n* Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1 (Appendix A)\n* Has received the final dose of any of the following treatments\u002F procedures within the specified minimum intervals before first dose of study drug:\n* Focal radiation therapy - 7 days\n* Surgery with general anesthesia - 7 days\n* Surgery with local anesthesia - 7 days\n* May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment.\n* May have received neoadjuvant chemotherapy with FOLFIRINOX if given at least 6 months before study enrollment.\n* May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if given at least 6 months before study enrollment.\n* Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal AND barrier method of birth control, or true abstinence) for the duration of study participation and in the following 9 months after discontinuation of study treatment.\n* Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 9 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence.\n* Must not be receiving any other investigational medicinal product.\n\nExclusion Criteria:\n\n* Is pregnant or lactating.\n* Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor.\n* History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent.\n* Has endocrine or acinar pancreatic carcinoma.\n* Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).\n* Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening.\n* Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the treating investigator or PI.\n* Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug.\n* Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered). In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major.\n* Has any medical and\u002For social condition that, in the opinion of the investigator would preclude study participation.\n* Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.\n* Has a current malignancy other than pancreatic cancer.\n* Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent).\n* Physiologic corticosteroid replacement therapy at doses \\> 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.\n* Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.\n* Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.\n* Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment-related standard premedication are permitted.\n* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.\n* Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is \\> 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids for this purpose, and not have had radiation pneumonitis.\n* Has received systemic antibiotics ≤ 7 days prior to the first dose of study drug.\n* History of organ transplant, including allogeneic stem cell transplantation.\n* Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).\n* Known allergy or hypersensitivity to any component of retifanlimab or formulation components.\n* Has received a live vaccine within 28 days of the planned start of study drug.\n* Patients with known history of UGT1A1 gene polymorphism.","ALL","18 Years",{"count":20,"type":21},12,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This is a study of the combination of 9 ING-41 (elraglusib) and retifanlimab plus mFOLFIRINOX in patients with pancreatic cancer without prior systemic therapy for advanced disease. The safety lead-in cohort will consist of 6 patients, followed by dose de-escalation if necessary, based on safety assessments. After evaluating the safety and tolerability at the initial dose level, the study will proceed to an expansion cohort at the determined safe dose level, with the total maximum enrollment not exceeding 12 patients for the entire study.",[27],"Pancreatic Adenocarcinoma",[29,30],"Glycogen Synthase Kinase 3-beta (GSK-3β) inhibitor","PD-1 inhibitor","RECRUITING","2026-09-22",{"date":34,"type":35},"2026-09-24","ACTUAL",{"date":37,"type":35},"2025-09-22",{"date":39,"type":21},"2029-12-31",{"name":41,"class":42},"Anwaar Saeed","OTHER",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":50,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":56,"conditions":57,"keywords":62,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":67,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":74},"100327187","phase-1-cabozantinib-plus-durvalumab-with-or-without-tremelimumab-in-patients-with-gastroesophageal-cancer-and-other-gastrointestinal-malignancies-100327187","NCT03539822","Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies","A Phase I\u002FII Trial of Cabozantinib in Combination With Durvalumab (MEDI4736) With or Without Tremelimumab in Patients With Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)","CAMILLA","Inclusion Criteria:\n\n1. Age ≥ 18 years\n2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1\n3. Histologically confirmed diagnosis of any of the following:\n\n   • Gastric or gastroesophageal junction adenocarcinoma\n   * Esophageal adenocarcinoma\n   * Colorectal adenocarcinoma (CRC)\n   * Hepatocellular carcinoma (HCC)\n4. Patients should have advanced (stage 4) or locally unresectable (stage III) disease.\n5. Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1\n6. Patients must consent to undergo a required screening\u002Fbaseline biopsy procedure (and potentially another tumor biopsy at time of disease response and progression) for correlative testing.\n7. Patients with gastric, gastroesophageal, or esophageal adenocarcinoma must show evidence of progression or intolerance to at least one previous standard of care systemic therapy.\n8. Patients with CRC must show evidence of progression or intolerance to at least 2 previous standard of care systemic therapy. Ras wild type patients should fail epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab or cetuximab) to be eligible.\n\n10\\. For cohort 3: Patients with HCC must show evidence of disease progression or intolerance to at least 1 previous systemic regimen (not more than 2 lines of prior therapy).\n\n11\\. For cohort 4: Patients with HCC must be treatment naïve or show evidence of disease progression or intolerance to at least 1 previous systemic regimen (not more than 2 lines of prior therapy).\n\n12\\. Patients should have known tumor results for microsatellite instability (MSI) or mismatch repair (MMR) proteins. If unknown, analysis will be obtained through local pathology lab using archival tissue if available or the baseline tumor biopsy.\n\n13\\. Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments unless AE(s) are clinically nonsignificant and\u002For stable on supportive therapy.\n\n14\\. Body weight \\> 66 lbs (30 kg) 15. Adequate organ and marrow function. 16. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.\n\n17\\. Women of child-bearing potential and men with partners of child-bearing potential must agree to use the highly effective forms of contraception prior to study entry, for the duration of study participation, and for 180 Days post completion of therapy. Men of child-bearing potential must not donate sperm while on this study and for 180 Days after their last study treatment.\n\nExclusion Criteria:\n\n1. Prior treatment with a Programmed cell death protein 1 (PD1) or (PD-L1) inhibitor, including durvalumab, or anti PD-L2 (HCC and gastric \u002F esophageal cancer patients with prior exposure to these agents are eligible).\n2. Prior treatment with cabozantinib or other Receptor for hepatocyte growth factor (MET) or Dual MET\u002F Hepatocyte growth factor (HGF) monoclonal antibodies or MET\u002FHGF tyrosine kinase inhibitors (TKIs), including crizotinib, foretinib, tivantinib, rilotumumab, and onartuzumab.\n3. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.\n\n   \\* Evidence of tumor invading the GI tract, (Defined as T4 primary tumor in patients with gastric, gastroesophageal and esophageal adenocarcinoma and CRC).\n\n   \\* Gastric or esophageal varices that are untreated or incompletely treated with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible.\n4. Evidence of active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.\n5. Inability to swallow tablets.\n6. Uncontrollable ascites or pleural effusion.\n7. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.\n8. Clinically significant hematuria, hematemesis, or hemoptysis of \\>0.5 tsp (2.5ml) of red blood, or other history of significant bleeding within 12 weeks.\n\n   \\* Any sign indicative of pulmonary hemorrhage within 3 months.\n\n   \\* Lesions invading any major blood vessels. HCC subjects with lesions invading the hepatic portal vasculature are eligible.\n9. Any unresolved toxicity CTCAE Grade ≥2 from previous anticancer therapy\n10. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug\n11. Major surgery (eg, Gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment.\n12. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses.\n13. History of allogenic organ transplantation.\n14. Active or prior documented autoimmune or inflammatory disorders\n15. History of active primary immunodeficiency\n16. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. HCC patients with hepatitis B or C infection are allowed per protocol specific criteria.\n17. Receipt of live attenuated vaccine within 30 days prior to the first dose.\n18. Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 millimeter of mercury (mm Hg) systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n19. Stroke, including transient ischemic attack (TIA), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose. Participants with a diagnosis of deep venous thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with Low Molecular Weight Heparin (LMWH) for at least 2 weeks before first dose.\n20. Has untreated central nervous system (CNS) metastases and\u002For carcinomatous meningitis\n21. Clinically significant disorders that would preclude safe study participation.\n22. History of another primary malignancy except for:\n\n    * Malignancy treated with curative intent\u002F resection and with no known active disease before the first dose of investigational product (IP) and of low potential risk for recurrence.\n    * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.\n    * Adequately treated carcinoma in situ without evidence of disease.\n\n24\\. Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n\n1. Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.\n2. Low-dose (prophylactic) low molecular weight heparins (LMWH) are permitted.\n3. Anticoagulation with therapeutic doses of LMWH is allowed in subjects with no known brain metastases, clinically significant hemorrhage, or complications from a thromboembolic event on the anticoagulation regimen (subjects with HCC must also have a screening platelet count \\>100,000\u002Fμl), and who have been on a stable dose of LMWH for at least 1 week before first dose.\n\n   25\\. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.",{"count":53,"type":21},117,[24,55],"PHASE2","The investigators propose to evaluate the safety of drug combinations in patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies for patients with advanced gastric cancer and other GI malignancies is an area of great unmet need. The investigators believe that modulating the tumor microenvironment with biologic agents like cabozantinib will have synergistic effect when combined with checkpoint-based immunotherapeutics like durvalumab in this patient population. This is a phase I\u002FII, open label, multi-cohort trial looking at safety, tolerability and efficacy endpoints.",[58,59,60,61],"Gastric Cancer","Esophageal Adenocarcinoma","Hepatocellular Carcinoma","Colorectal Cancer",[63,64,65],"Cabozantinib","Durvalumab","Tremelimumab","2026-01-16",{"date":68,"type":35},"2026-01-21",{"date":70,"type":35},"2018-10-22",{"date":72,"type":21},"2029-06-30",{"name":41,"class":42},2,{"id":76,"slug":77,"hasResults":11,"nctId":78,"briefTitle":79,"officialTitle":80,"acronym":81,"eligibilityCriteria":82,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":83,"targetDuration":4,"studyType":22,"phases":85,"briefSummary":86,"conditions":87,"keywords":88,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":93,"lastUpdatePostDateStruct":94,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":5},"100569746","phase-2-zanzalintinib-xl-092-plus-durvalumab-and-tremelimumab-in-unresectable-hepatocellular-carcinoma-zenobia-100569746","NCT06698250","Zanzalintinib (XL-092) Plus Durvalumab and Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)","Phase II Trial of Zanzalintinib (XL-092) in Combination With Durvalumab Plus Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)","ZENOBIA","Inclusion Criteria:\n\n1. Patients must have unresectable hepatocellular carcinoma.\n2. Patients must be treatment naïve for systemic therapy in the unresectable setting.\n3. ≥ 18 years and ECOG performance status 0-1\n4. Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), unless AE(s) are clinically nonsignificant and\u002For stable on supportive therapy (e.g., physiological replacement of mineralocorticosteroid).\n5. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment.\n6. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg\u002Fmg (≤ 113.2 mg\u002Fmmol) creatinine. Tumor tissue fresh biopsies are REQUIRED for ALL study participants at screening\u002Fbaseline unless an archival tumor tissue block is available and fulfills the criteria\n\n   • Note that PI approval can be obtained if institution is unable to release blocks.\n7. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.\n8. Sexually active fertile subjects and their partners must agree to use highly effective method of contraception prior to study entry, during the course of the study, and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.\n9. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless permanent sterilization or documented postmenopausal status criteria are met.\n\nExclusion Criteria:\n\n1. Prior treatment with XL092, or PD-1\u002FPD-L1 or CTLA-4 inhibitors.\n2. Receipt of any type of small molecule kinase inhibitor such as cabozantinib or other MET or Dual MET\u002FHGF monoclonal antibodies or MET\u002FHGF tyrosine kinase inhibitors (TKIs), or any other VEGFR TKIs (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.\n3. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.\n4. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.\n\n   Note: Subjects with an incidental finding of an isolated brain lesion \\\u003C 1 cm in diameter may be eligible after Principal Investigator approval if the lesion is radiographically stable for 4 weeks before first dose and does not require treatment per Investigator judgement.\n\n   Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.\n6. Concomitant anticoagulation with oral anticoagulants (e.g., warfarin and direct thrombin inhibitors) and platelet inhibitors (e.g., clopidogrel).\n\n   Note: Allowed anticoagulants are low-dose aspirin for cardioprotection (per local applicable guidelines) and low molecular weight heparins (LMWH). Therapeutic doses of LMWH are not permitted in subjects with known brain metastases. Subjects treated with therapeutic LMWH must have a screening platelet count \\> 100,000\u002FμL. Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.\n7. Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.\n8. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n   a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes). ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction, or other clinically significant ischemic event within 12 months before first dose of study treatment. iv. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA\u002FTIA arterial thromboembolic events within 6 months before to first dose of study treatment. Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and treated with anticoagulation per standard of care before first dose of study treatment. Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator. v. Prior history of myocarditis. b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI-tract from external viscera\n\n   ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra- abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment. v. Known gastric or esophageal varices\n9. Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.\n10. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.\n11. Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Subjects with lesions invading the hepatic portal vasculature are eligible. Note: Subjects with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior V.\n\n    cava) may be eligible following Principal Investigator approval.\n12. Other clinically significant disorders that would preclude safe study participation.\n\n    1. Active infection requiring systemic treatment. Note: Prophylactic antibiotic treatment is allowed.\n    2. Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.\n    3. Known positive test for or suspected infection with SARS-CoV-2 within one month before enrollment. Note: demonstration that the subject has fully recovered from the infection is required to be eligible for enrollment\n    4. Serious non-healing wound\u002Fulcer\u002Fbone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.\n    5. Malabsorption syndrome.\n    6. Pharmacologically uncompensated, symptomatic hypothyroidism.\n    7. Moderate to severe hepatic impairment (Child-Pugh B or C).\n    8. Requirement for hemodialysis or peritoneal dialysis.\n    9. History of solid organ or allogeneic stem cell transplant.\n13. Major surgery within 8 weeks prior to first dose of study treatment. Prior laparoscopic nephrectomy within 4 weeks prior to first dose of study treatment. Minor surgery within 10 days before the first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.\n\n    Note: Fresh tumor biopsies should be performed at least 7 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.\n14. Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 450 ms for males or \\> 470 for females within 14 days per electrocardiogram (ECG) before first dose of study treatment.\n\n    Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.\n15. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.\n16. Pregnant or lactating females.\n17. Inability to swallow tablets.\n18. Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n19. Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.\n20. Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.\n21. Any active, known or suspected autoimmune disease requiring long term treatment with immunosuppressive medications. Note: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n22. Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease.\n23. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n24. Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after Principal Investigator approval.\n25. Diagnosis of immunodeficiency or is receiving systemic steroid therapy (\\> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Inhaled, intranasal, intraarticular, and topical corticosteroids and mineralocorticoids are allowed. Note: Adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Transient short-term use of higher doses of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed.\n26. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.\n27. Documented hepatic encephalopathy (HE) within 6 months before first dose of study treatment.\n28. Clinically meaningful ascites (i.e., ascites requiring paracentesis or escalation in diuretics) within 6 months before first dose of study treatment.\n29. Subjects who have received any local anticancer therapy including surgery, regional ablative therapies including thermal ablation, radiofrequency ablation (RFA), Microwave Ablation (MWA) transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to first dose of study treatment.\n30. Child Pugh score \\> 7.",{"count":84,"type":21},40,[55],"This study will investigate if modulating the tumor microenvironment with biologic agents like XL-092 will have synergistic effect when combined with checkpoint based immunotherapeutic treatment of patients with hepatocellular carcinoma (HCC).",[60],[89,90,91,92],"tyrosine kinase inhibitor (TKI)","vascular endothelial growth factor (VEGF)","AXL receptor tyrosine kinase (AXL)","Programmed death-1\u002Fprogrammed death ligand-1 (PD-1\u002FPD-L1)","2025-11-04",{"date":95,"type":35},"2025-11-06",{"date":97,"type":35},"2024-12-18",{"date":99,"type":21},"2027-04-30",{"name":41,"class":42},""]