[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100649600":3},{"organization":4,"armGroups":7,"interventions":25,"overallOfficials":31,"centralContacts":44,"locations":53,"responsibleParty":66,"collaborators":31,"id":70,"slug":71,"hasResults":72,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":31,"eligibilityCriteria":76,"healthyVolunteers":72,"sex":77,"minAge":78,"maxAge":31,"enrollmentInfo":79,"targetDuration":31,"studyType":82,"phases":83,"briefSummary":86,"conditions":87,"keywords":31,"overallStatus":90,"whyStopped":31,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":95,"completionDateStruct":97,"leadSponsor":99,"locationsCount":100},{"fullName":5,"class":6},"Zhejiang University","OTHER",[8,15,20],{"label":9,"type":10,"description":11,"interventionNames":12},"Arm A","EXPERIMENTAL","This arm evaluates HRS-2329 in combination with nimotuzumab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who have received at least one prior line of therapy. Approximately 6 to 10 participants are planned to be enrolled initially to assess safety and preliminary efficacy, at the prespecified dose of HRS-2329 240 mg QD plus nimotuzumab 400 mg (D1,D8,Q3W). If the safety at this dose level is acceptable, enrollment may be expanded to 15-20 participants. During this period, the Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.",[13,14],"Drug: HRS-2329 Tablet","Drug: Nimotuzumab",{"label":16,"type":10,"description":17,"interventionNames":18},"Arm B","This arm evaluates HRS-2329 and HS-20093 with or without nimotuzumab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who are treatment-naïve or have received up to one prior line of standard systemic therapy. Approximately 30 participants are planned to be enrolled. The prespecified doses are HRS-2329 240 mg QD plus HS-20093 8.0 mg\u002Fkg Q3W, with or without nimotuzumab 400 mg on Day 1 and Day 8 of each 3-week cycle. The Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.",[13,14,19],"Drug: HS-20093",{"label":21,"type":10,"description":22,"interventionNames":23},"Arm C","Alternative arm: This arm evaluates HRS-2329 and HS-20093 in combination with adebrelimab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who are treatment-naïve or have received up to one prior line of standard systemic therapy. Approximately 30 participants are planned to be enrolled. The prespecified doses are HRS-2329 240 mg QD plus HS-20093 8.0 mg\u002Fkg Q3W plus adebrelimab 1200 mg Q3W. The Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.",[13,19,24],"Drug: Adebrelimab",[26,32,36,40],{"type":27,"name":28,"description":29,"armGroupLabels":30,"otherNames":31},"DRUG","HRS-2329 Tablet","HRS-2329 is a novel, potent, oral pan-RAS inhibitor that demonstrates strong inhibitory activity against a broad range of RAS-related targets, including KRAS G12V, KRAS G12C, KRAS G12D, KRAS wild-type, NRAS, and HRAS. HRS-2329 forms a ternary complex with Cyclophilin A (CypA) and the target, thereby blocking the binding of RAS-GTP to downstream proteins and disrupting downstream signaling pathways. This ultimately inhibits tumor cell proliferation and exerts anti-tumor effects.\n\nHRS-2329 240 mg is given orally (to be swallowed whole, not chewed) once daily on a 3-week cycle. It should be taken orally within 30 minutes after breakfast each morning.",[9,16,21],null,{"type":27,"name":33,"description":34,"armGroupLabels":35,"otherNames":31},"Nimotuzumab","Nimotuzumab is a marketed drug, a recombinant humanized monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Nimotuzumab is administered at 400 mg by intravenous infusion over at least 60 minutes on Days 1 and 8 of each 3-week cycle.",[9,16],{"type":27,"name":37,"description":38,"armGroupLabels":39,"otherNames":31},"HS-20093","HS-20093 is a B7-H3 antibody-drug conjugate (ADC) composed of the HS-20093 naked antibody (HS-20093 Ab) and a small-molecule toxin (HS-9265, also known as SHR169265) conjugated via a cleavable tetrapeptide linker. The anti-B7-H3 antibody is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb), and the small-molecule toxin, an exatecan derivative, is a topoisomerase I inhibitor. HS-20093 injection is administered at 8.0 mg\u002Fkg by intravenous infusion on Day 1 of each 3-week cycle.",[16,21],{"type":27,"name":41,"description":42,"armGroupLabels":43,"otherNames":31},"Adebrelimab","Adebrelimab is a recombinant humanized anti-PD-L1 monoclonal antibody injection. It specifically blocks the binding of PD-1 to PD-L1, thereby terminating the immunosuppressive signals transmitted through PD-1 to T cells. This enables T cells to re-recognize tumor cells and exert cytotoxic effects, ultimately inhibiting tumor growth. Adebrelimab injection is administered at 1200 mg by intravenous infusion on Day 1 of each 3-week cycle.",[21],[45,50],{"name":46,"role":47,"phone":48,"phoneExt":31,"email":49},"Tingbo Liang, MD.","CONTACT","+86 19941463683","liangtingbo@zju.edu.cn",{"name":51,"role":47,"phone":31,"phoneExt":31,"email":52},"Yiwen Chen, MD.","yiwenchen0705@126.com",[54],{"facility":55,"status":31,"city":56,"state":57,"zip":31,"country":58,"countryCode":59,"cosmosGeoPoint":60,"geoPoint":65,"contacts":31},"the First Affiliated Hospital, School of Medicine","Hangzhou","Zhejiang","China","CN",{"type":61,"coordinates":62},"Point",[63,64],120.16142,30.29365,{"lat":64,"lon":63},{"type":67,"investigatorFullName":68,"investigatorTitle":69,"investigatorAffiliation":5,"oldNameTitle":31,"oldOrganization":31},"PRINCIPAL_INVESTIGATOR","TingBo Liang","The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine","100649600","phase-1-a-pan-ras-inhibitor-in-combination-with-anti-tumor-therapy-in-participants-with-advanced-pancreatic-cancer-100649600",false,"NCT07736612","A Pan-RAS Inhibitor in Combination With Anti-Tumor Therapy in Participants With Advanced Pancreatic Cancer","A Phase Ib\u002FII Study of the Safety, Tolerability, and Efficacy of a Pan-RAS Inhibitor in Combination With Anti-Tumor Therapy in Participants With Advanced Pancreatic Cancer","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Histopathologically confirmed locally advanced or metastatic pancreatic adenocarcinoma (originating from pancreatic ductal epithelium) that is not amenable to curative therapy.\n* RAS mutation or amplification detected in tumor tissue or blood (by RAS testing).\n* Prior anti-tumor therapy:\n\n  1. For cohort HRS-2329-A: at least one line of standard systemic therapy in the advanced setting;\n  2. For cohorts HRS-2329-B and HRS-2329-C: at most one line of standard systemic therapy in the advanced setting.\n* At least one measurable lesion according to RECIST version 1.1 criteria.\n* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.\n* Life expectancy ≥ 3 months.\n* Adequate function of vital organs.\n* Use of appropriate contraceptive methods during the study period, and so forth.\n* Voluntary participation in this study with signed informed consent, good compliance, and willingness to cooperate with follow-up assessments.\n\nExclusion Criteria:\n\n* Prior treatment with drugs similar to the investigational product.\n* Known presence of central nervous system (CNS) metastases.\n* Acute or chronic pancreatitis requiring clinical intervention.\n* Gastrointestinal disorders that may affect drug administration\u002Fabsorption, including but not limited to dysphagia, malabsorption syndrome, refractory nausea, vomiting, or diarrhea, Crohn's disease, and ulcerative colitis.\n* Gastrointestinal obstruction, or signs\u002Fsymptoms of gastrointestinal obstruction; however, patients who have undergone surgical intervention with complete resolution of the obstruction may be considered for screening.\n* Concurrent biliary obstruction with risk of biliary tract infection (patients with treatable biliary obstruction may be enrolled if adequate biliary drainage is achieved and the risk of biliary infection is resolved after treatment).\n* Third-space fluid collections (e.g., massive pleural effusion, ascites) that cannot be stabilised (i.e., no intervention required after drainage removal) within 2 weeks prior to enrolment; patients with only a small amount of fluid detected by imaging and without clinical symptoms may be enrolled.\n* Severe infection within 4 weeks prior to enrolment, such as severe pneumonia, bacteraemia, or infectious complications requiring hospitalisation; unexplained fever \\>38.5°C within 2 weeks prior to enrolment ; signs\u002Fsymptoms of infection requiring intravenous antibiotic therapy within 2 weeks prior to enrolment.\n* Severe cardiovascular or cerebrovascular diseases.\n* Known or suspected interstitial lung disease (isolated imaging findings of interstitial changes are not excluded).\n* History of definite neurological or psychiatric disorders, including epilepsy and dementia.\n* Non-healing wounds (severe, non-healing, or dehiscent), or unhealed fractures.\n* Adverse events from prior therapy not recovered to NCI-CTCAE Grade ≤1 at enrolment .\n* History of malignancies other than the primary tumour within 5 years prior to enrolment, with the exception of malignancies with low risk of metastasis and death, such as adequately treated carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin.\n* Active hepatitis B infection.\n* For Cohort C, conditions that are unsuitable for immunotherapy.\n* Known allergy to any component of any of the study drugs to be administered.\n* Any other condition that, in the investigator's judgement, may affect the study results or result in premature termination of the study.","ALL","18 Years",{"count":80,"type":81},80,"ESTIMATED","INTERVENTIONAL",[84,85],"PHASE1","PHASE2","This study aims to evaluate the safety, tolerability, and efficacy of HRS-2329 in combination with other anti-tumor therapies in participants with advanced pancreatic cancer harboring RAS mutations or amplifications.",[88,89],"Pancreatic Cancer","RAS Mutations or Amplifications","NOT_YET_RECRUITING","2026-07-27",{"date":93,"type":94},"2026-07-30","ACTUAL",{"date":96,"type":81},"2026-08-15",{"date":98,"type":81},"2029-12-30",{"name":5,"class":6},1]