[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"braf\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:braf":34},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,92],{"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":25,"conditions":26,"keywords":59,"overallStatus":79,"whyStopped":4,"lastUpdateSubmitDate":80,"lastUpdatePostDateStruct":81,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":91},"100499720","phase-1-phase-12-trial-of-s241656-in-selected-rasmapk-mutation--positive-malignancies-100499720",false,"NCT05786924","Phase 1\u002F2 Trial of S241656 in Selected RAS\u002FMAPK Mutation- Positive Malignancies","A Phase 1\u002F2, Open-label Study of Oral S241656 (BDTX-4933) as Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With KRAS, BRAF and Other Selected RAS\u002FMAPK Mutation-Positive Malignancies","Key Inclusion Criteria:\n\n* Life expectancy of ≥ 12 weeks in the opinion of the investigator.\n* Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.\n* Adequate bone marrow and organ function.\n* Recovered from toxicity to prior anti-cancer therapy.\n\nPart 1 Dose Escalation cohort ONLY:\n\n* Part 1A: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations\n* Part 1B: Advanced\u002Fmetastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1C: Advanced\u002Fmetastatic PDAC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1E: Other advanced\u002Fmetastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations\n\nPart 2 Dose Optimization and Expansion cohorts ONLY:\n\n* Part 2A: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C mutations and\u002For BRAF mutations\n* Part 2A1: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C mutations\n* Part 2A2: Advanced\u002Fmetastatic NSCLC with BRAF mutations\n* Part 2A3: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease\n* Part 2A4: Advanced\u002Fmetastatic NSCLC with a KRAS G12C mutation\n* Part 2B1: Advanced\u002Fmetastatic PDAC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 2B2: Advanced\u002Fmetastatic CRC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 2B3: Advanced\u002Fmetastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n\nKey Exclusion Criteria:\n\n* Cancer that has a known MEK1\u002F2 mutation.\n* Known allergy\u002Fhypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.\n* Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.\n* Major surgery within 4 weeks of study entry or planned during study.\n* Ongoing anticancer therapy.\n* Ongoing radiation therapy.\n* Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.\n* Clinically significant cardiovascular disease.\n* Symptomatic spinal cord compression.\n* Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.\n* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.\n* Females who are pregnant or breastfeeding.\n* Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.\n* Prior use of experimental agents that target the KRAS\u002FBRAF\u002FMEK\u002FERK pathway.","ALL","18 Years",{"count":19,"type":20},554,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","BDTX-4933-101 is a first-in-human, open-label, Phase 1\u002F2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced\u002Fmetastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced\u002Fmetastatic NSCLC with KRAS and\u002For BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.",[27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58],"Non-small Cell Lung Cancer","Histiocytic Neoplasm","Histiocytosis","BRAF Gene Mutation","BRAF V600E","BRAF V600 Mutation","BRAF Mutation-Related Tumors","BRAF","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Lung Cancer","Recurrent Lung Cancer","Recurrent Lung Non-Small Cell Carcinoma","NSCLC","Solid Tumor","Solid Carcinoma","KRAS G12D","KRAS G12V","KRAS Mutation-Related Tumors","NRAS Gene Mutation","Thyroid Cancer","Thyroid Carcinoma","Colorectal Cancer","Colorectal Carcinoma","Recurrent Histiocytic and Dendritic Cell Neoplasm","Brain Metastases","Recurrent NSCLC","KRAS G13C","Acquired Resistance to KRAS G12C Inhibitor","KRAS G12A","KRAS G12F","KRAS G12R","KRAS G13D",[60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78],"BRAF Class I","BRAF Class II","BRAF Class III","KRAS","Intolerant histiocytic neoplasm","BDTX-4933","Phase 1","dose escalation","dose expansion","MAPK","mitogen-activated protein kinase","RAS","RAF","Upstream oncogenic alterations","RAF inhibitor","intracranial disease","CRAF","NRAS","RAF fusions","RECRUITING","2026-06-16",{"date":82,"type":83},"2026-06-17","ACTUAL",{"date":85,"type":83},"2023-04-18",{"date":87,"type":20},"2028-06",{"name":89,"class":90},"Institut de Recherches Internationales Servier","OTHER",27,{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":96,"acronym":97,"eligibilityCriteria":98,"healthyVolunteers":11,"sex":16,"minAge":99,"maxAge":100,"enrollmentInfo":101,"targetDuration":4,"studyType":21,"phases":103,"briefSummary":104,"conditions":105,"keywords":109,"overallStatus":79,"whyStopped":4,"lastUpdateSubmitDate":115,"lastUpdatePostDateStruct":116,"startDateStruct":118,"completionDateStruct":120,"leadSponsor":122,"locationsCount":124},"100612751","phase-2-the-safety-and-efficacy-of-cetuximab-beta-plus-fruquintinib-with-or-without-immune-checkpoint-inhibitorrs-in-first-line-treatment-of-rasbraf-wild-type-unresectable-metastatic-colorectal-cancer-100612751","NCT07257653","The Safety and Efficacy of Cetuximab Beta Plus Fruquintinib With or Without Immune Checkpoint Inhibitorrs in First-line Treatment of RAS\u002FBRAF Wild Type Unresectable Metastatic Colorectal Cancer","concept","Inclusion Criteria:\n\n1）Subjects voluntarily join this study, sign the informed consent form, and demonstrate good compliance; 2) Age: 10-80 years old, ECOG PS score of 0-1. For patients aged 80-85, comprehensive functional assessments must be completed, and they may be enrolled if the investigator deems them tolerable, with an expected survival of over 3 months; 3) Histopathologically and\u002For cytologically confirmed, unresectable metastatic colorectal adenocarcinoma confirmed by MDT discussion (UICC\u002FAJCC TNM staging system for colorectal cancer, 8th Edition, 2017); 4) At least one measurable lesion confirmed according to RECIST 1.1 criteria; 5) Adequate function of major organs, meeting the following criteria:\n\n1. Hematological examination standards (no blood transfusion or use of hematopoietic growth factors for correction within 7 days prior to screening):\n\n   1. Hemoglobin (HGB) ≥ 90 g\u002FL;\n   2. Absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹\u002FL;\n   3. Platelet count (PLT) ≥ 75 × 10⁹\u002FL;\n2. Biochemical tests must meet the following criteria:\n\n   1. Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3 × ULN for subjects with Gilbert's syndrome);\n   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. If with liver metastases, ALT and AST ≤ 5 × ULN;\n   3. Serum creatinine (CR) ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 50 ml\u002Fmin.\n3. Coagulation function or thyroid function tests must meet the following criteria:\n\n   1. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5 × ULN (without anticoagulant therapy);\n   2. Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be assessed (FT3 and FT4 may be substituted if T3\u002FT4 are unavailable at the center). Subjects may be enrolled if T3 and T4 levels are normal.\n4. Echocardiogram assessment: Left ventricular ejection fraction (LVEF) ≥ 50%.\n5. Hepatitis B surface antigen (HBsAg) negative. If HBsAg positive, hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be \\\u003C 2500 copies\u002FmL or 500 IU\u002FmL for enrollment.\n6. HCV antibody negative or HCV-RNA negative subjects may enroll; if HCV-RNA positive, subjects must have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN to enroll. Subjects with co-infection of hepatitis B and hepatitis C are excluded (positive for HBsAg or HBcAb, and positive for HCV antibody).\n7. Female patients must meet one of the following conditions:\n\n   1. Postmenopausal (defined as no menses for at least 1 year, with no other confirmed causes besides menopause), or\n   2. Surgically sterilized (removal of ovaries and\u002For uterus), or\n   3. Of childbearing potential but must meet the following:\n\n      * Serum\u002Furine pregnancy test within 7 days prior to enrollment must be negative;\n      * Agree to use contraception with a failure rate of \\\u003C 1% per year or maintain abstinence (avoiding heterosexual intercourse) (from signing the ICF until at least 6 months after the last dose of the study drug) (contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, copper intrauterine devices, or condoms);\n      * Must not be breastfeeding.\n8. Male patients must meet the following: Agree to abstinence (avoiding heterosexual intercourse) or use contraception, as specified: When the partner is a woman of childbearing potential or is pregnant, the male patient must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose to prevent fetal drug exposure. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.\n\nExclusion Criteria:\n\n1. Presence of MSI-H\u002FdMMR patients.\n2. Concurrent diseases and medical history:\n\n   1. Diagnosis of or concurrent other malignancies within the past 3 years. The following conditions are eligible for enrollment:\n\n      Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \\[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)\\];\n   2. Multiple factors affecting oral medication (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);\n   3. History or tendency of gastrointestinal bleeding or perforation within 4 weeks prior to enrollment;\n   4. Patients with active inflammatory bowel disease within 4 weeks prior to enrollment;\n   5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;\n   6. Unresolved toxicities from any prior antitumor therapy exceeding CTCAE Grade 1 (excluding alopecia and oxaliplatin-induced neurotoxicity ≤ Grade 2);\n   7. Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of study treatment (excluding gastrointestinal endoscopic biopsy);\n   8. Symptoms of active bleeding within 1 week prior to screening, without significant improvement or control;\n   9. Patients with any bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to study initiation, or presence of unhealed wounds, ulcers, or fractures;\n   10. Arterial\u002Fvenous thrombotic events within 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;\n   11. History of psychoactive drug abuse with inability to abstain;\n   12. Patients with any severe and\u002For uncontrolled diseases, including:\n\n       * Uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after standard antihypertensive therapy);\n       * Myocardial ischemia ≥ Grade 2, myocardial infarction, arrhythmias (including QTc ≥450 ms for males, QTc ≥470 ms for females), and congestive heart failure ≥ Grade 2 (New York Heart Association (NYHA) classification);\n       * Active or uncontrolled severe infections (≥ CTCAE Grade 2 infection);\n       * Liver cirrhosis, active hepatitis\\*; (\\*Active hepatitis \\[Hepatitis B reference: HBsAg positive and HBV DNA positive (\\>2500 copies\u002FmL or \\>500 IU\u002FmL); Hepatitis C reference: HCV antibody positive and HCV viral titer above the upper limit of normal\\]. Note: Eligible HBsAg-positive or HBcAb-positive subjects and hepatitis C patients require continuous antiviral therapy to prevent viral reactivation.)\n       * Renal failure requiring hemodialysis or peritoneal dialysis;\n       * History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;\n       * Poorly controlled diabetes (fasting blood glucose \\>10 mmol\u002FL);\n       * Urinalysis showing urine protein ≥++ and confirmed 24-hour urine protein quantification \\>1.0 g;\n       * History of clear neurological or psychiatric disorders, including epilepsy or dementia requiring treatment.\n   13. Patients with known active or suspected autoimmune diseases. Patients with immune-related hypothyroidism requiring thyroid hormone replacement therapy and well-controlled type I diabetes are allowed. Patients with vitiligo requiring no intervention or resolved childhood asthma\u002Fallergies requiring no intervention in adulthood are allowed.\n\n       * Receipt of live vaccines within 28 days prior to enrollment. However, inactivated viral vaccines for seasonal influenza are permitted, while live attenuated influenza vaccines administered intranasally are not allowed.\n       * Patients requiring systemic glucocorticoids (\\>10 mg\u002Fday prednisone equivalent) or other immunosuppressive drugs within 14 days prior to enrollment or during the study. The following conditions are allowed for enrollment:\n       * Use of topical or inhaled glucocorticoids in the absence of active autoimmune diseases;\n       * Adrenal glucocorticoid replacement therapy at doses ≤10 mg\u002Fday prednisone equivalent.\n   14. Participation in other clinical studies or initiation of study treatment within 14 days after the end of prior clinical study treatment. History of severe allergy to any monoclonal antibody.\n3. Tumor-related symptoms and treatment:\n\n   1. Surgery (excluding prior diagnostic biopsies), radiotherapy, chemotherapy, or other anticancer therapies within 4 weeks prior to the start of study treatment (calculated from the end date of the last treatment as the washout period);\n   2. Prior postoperative adjuvant therapy containing anti-angiogenic targeted drugs (including bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, etc.);\n\n   d) Patients with symptomatic brain metastases or those whose symptoms have been controlled for less than 2 months;\n4. Patients deemed by the investigator to have concomitant diseases that seriously endanger subject safety or affect study completion, or who are otherwise considered unsuitable for enrollment.","10 Years","85 Years",{"count":102,"type":20},70,[24],"Colorectal cancer is a malignant tumor ranking among the top four in incidence and the top three in causes of death globally . Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies is currently the standard first-line treatment for advanced pMMR colorectal cancer. The inclusion of anti-EGFR or anti-VEGF targeted therapies has improved the overall survival of advanced colorectal cancer patients from 13 months in the era of fluorouracil monotherapy to the current 30 months.\n\nHowever, many patients refuse chemotherapy or cannot tolerate cytotoxic chemotherapeutic drugs, which often leads to poor prognosis in advanced colorectal cancer. Thus, in the treatment of advanced colorectal cancer, is it possible to achieve antitumor activity through the combination of targeted drugs while avoiding chemotherapy?\n\nEarly clinical studies evaluated the possibility of combining anti-EGFR and anti-VEGF monoclonal antibodies. Subsequent large-scale Phase III clinical studies, such as PACCE , indicated that the combination of FOLFOX or FOLFIRI regimens with bevacizumab and panitumumab increased adverse reactions without providing survival benefits in the overall colorectal cancer population compared to the control group. Following this, the CAIRO2 clinical study added cetuximab to CapeOX combined with bevacizumab and still did not demonstrate survival benefits in the first-line treatment of advanced colorectal cancer, particularly in patients with RAS mutations. However, subgroup analyses suggested a certain survival advantage in patients with wild-type RAS who received combined targeted therapy. A recent clinical study (ECOG-ACRIN E7208) showed that in patients with KRAS wild-type advanced colorectal cancer, second-line use of irinotecan combined with cetuximab and ramucirumab significantly improved progression-free survival (PFS) and disease control rate (DCR) compared to cetuximab combined with irinotecan. These studies suggest that combining anti-EGFR and anti-VEGF monoclonal antibodies is a feasible approach for patients with wild-type RAS\n\nCertainly, in terms of anti-VEGF options, besides macromolecular anti-VEGFR monoclonal antibodies, small-molecule tyrosine kinase inhibitors targeting VEGF have also demonstrated significant antitumor activity in colorectal cancer. Studies have shown that fruquintinib significantly prolongs the survival of patients with advanced colorectal cancer, leading to its approval as a third-line treatment for colorectal cancer.\n\nOn the other hand, immunotherapy targeting PD-1 and CTLA-4 has recently made significant progress in the treatment of colorectal cancer. For the pMMR type, which accounts for over 90% of advanced colorectal cancer cases, related clinical studies have confirmed that the combination of immunotherapy and targeted therapy has significant antitumor synergistic effects. These studies also indicate that immune checkpoint inhibitors can enhance the antitumor activity of anti-EGFR and anti-VEGF targeted therapies in pMMR advanced colorectal cancer.\n\nThis study aims to evaluate the efficacy and safety of cetuximab combined with fruquintinib, with or without immune checkpoint inhibitors, as a first-line treatment for pMMR, RAS\u002FBRAF wild-type metastatic colorectal cancer.",[106,71,34,107,108],"Colorectal Neoplasms","Cetuximabβ","Fruquintinib",[110,111,112,113,114],"Colorectal cancer","Chemotherapy-free","KRAS\u002FNRAS\u002FBRAF wild-type","cetuximab combined with fruquintinib","with or without immune checkpoint inhibitors","2025-11-20",{"date":117,"type":83},"2025-12-02",{"date":119,"type":83},"2025-10-21",{"date":121,"type":20},"2027-12-31",{"name":123,"class":90},"Zhejiang University",1]