Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-29 @ 11:35 PM
Study NCT ID:
NCT07446335
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-03
First Post:
2026-02-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase III Study of First-line Anlotinib Combined With Benmelstobart in Patients With Advanced Esophageal Squamous Cell Carcinoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'interventionBrowseModule': {'meshes': [{'id': 'D004358', 'term': 'Drug Therapy'}], 'ancestors': [{'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 578}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2029-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-26', 'studyFirstSubmitDate': '2026-02-25', 'studyFirstSubmitQcDate': '2026-02-26', 'lastUpdatePostDateStruct': {'date': '2026-03-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'PFS', 'timeFrame': 'about 2 years', 'description': 'The time from randomization to the first occurrence of disease progression or death due to any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1.'}, {'measure': 'OS', 'timeFrame': 'about 2 years', 'description': 'The time from randomization to death due to any cause.'}], 'secondaryOutcomes': [{'measure': 'ORR', 'timeFrame': 'about 2 years', 'description': 'The percentage of subjects with complete response (CR) or partial response (PR) as determined by the investigator according to RECIST 1.1.'}, {'measure': 'DCR', 'timeFrame': 'about 2 years', 'description': 'The percentage of subjects with complete response (CR), partial response (PR), or disease stabilization (SD) for ≥6 weeks as determined by the investigator according to RECIST 1.1.'}, {'measure': 'DOR', 'timeFrame': 'about 2 years', 'description': 'The time from the first documented confirmed objective response to disease progression or death due to any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1.'}, {'measure': 'AE', 'timeFrame': 'about 2 years', 'description': 'The incidence and severity of adverse events, with severity graded according to the NCI CTCAE v5.0 scale.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Advanced Esophageal Squamous Cell Carcinoma']}, 'descriptionModule': {'briefSummary': 'A Randomized, Open-Label, Parallel-Controlled, Multicenter Phase III Clinical Trial to Evaluate the Safety and Efficacy of Anlotinib Hydrochloride Combined with Benmelstobart versus Toripalimab Combined with Chemotherapy as First-Line Treatment for Advanced Esophageal Squamous Cell Carcinoma Harboring Specific Gene Mutations'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* (1) Histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (excluding adenosquamous carcinoma); (2) No prior systemic therapy, or recurrence more than 6 months after completion of (neo)adjuvant therapy or definitive chemoradiotherapy; (3) Age: ≥18 years (calculated from the date of informed consent signature); ECOG PS score: 0-1; estimated life expectancy \\>3 months; (4) Presence of TP53 mutation or FAT1 mutation, and absence of NOTCH3 mutation; (5) At least one measurable lesion as confirmed by RECIST 1.1 criteria; measurable lesions should not have received prior local treatment such as radiotherapy (lesions within prior radiation fields may be selected as target lesions if progression is confirmed); (6) Adequate major organ function meeting the following criteria:\n* Hemoglobin ≥90 g/L;\n* Absolute neutrophil count (ANC) ≥1.5 × 10\\^9/L;\n* Platelets ≥75 × 10\\^9/L;\n* Total bilirubin ≤1.5 × upper limit of normal (ULN);\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if liver metastases present);\n* Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min;\n* Prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) ≤1.5 × ULN (for patients not receiving anticoagulation);\n* Thyroid-stimulating hormone (TSH) ≤ULN (if TSH abnormal, normal free T3 and free T4 are acceptable); (7) Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion, with negative serum or urine pregnancy test within 7 days prior to enrollment; men must agree to use effective contraception during the study and for 6 months after study completion, see Section 5.4 for details; (8) Voluntary participation in this study with signed informed consent and good compliance.\n\nExclusion Criteria:\n\n* (1) Other malignancies within 3 years prior to first dose or currently concurrent malignancies, except:Other malignancies treated with surgery alone with continuous disease-free survival (DFS) of ≥5 years;Cured cervical carcinoma in situ, non-melanomatous skin cancer, and superficial bladder tumors \\[Ta (non-invasive), Tis (carcinoma in situ), and T1 (tumor invades lamina propria)\\]; (2) Conditions affecting intravenous injection or blood collection, or factors affecting oral drug administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction); (3) Prior treatment-related adverse events not resolved to ≤Grade 1 per CTCAE v5.0, except Grade 2 alopecia, Grade 2 peripheral neuropathy, Grade 2 anemia, clinically non-significant and asymptomatic laboratory abnormalities, and hypothyroidism stable on hormone replacement therapy judged by investigator as having no safety risk; (4) Major surgery, significant traumatic injury within 4 weeks prior to first dose, or anticipated need for major surgery during study treatment (except protocol-required surgery), or presence of non-healing wounds or fractures. \\[Major surgery defined as Grade 3 or higher per National Surgical Classification Directory 2022\\]; (5) Esophageal squamous cell carcinoma with active bleeding from primary lesion within 2 months; hematemesis or melena with daily blood loss ≥2.5 mL within 3 months prior to screening, or any bleeding event ≥CTCAE Grade 3, or any bleeding signs or history regardless of severity judged by investigator as unsuitable for enrollment; (6) Arterial or venous thrombotic events within 6 months prior to first dose, including cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism; (7) Active viral hepatitis with inadequate control. Eligible if: HBsAg-positive subjects: HBV DNA \\<2000 IU/mL (or 1×10⁴ copies/mL) or receiving anti-HBV treatment for ≥1 week prior to study with ≥1 log reduction in viral load, with willingness to continue anti-HBV therapy throughout study; HCV-infected subjects (HCV Ab or HCV RNA positive): judged by investigator as stable or receiving approved antiviral treatment at enrollment with plan to continue; (8) Active syphilis infection requiring treatment; (9) Active tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, radiation pneumonitis requiring treatment, or symptomatic active pneumonia; (10) History of psychoactive substance abuse with inability to abstain, or psychiatric disorder; (11) Prior or planned allogeneic bone marrow or solid organ transplantation; (12) History of hepatic encephalopathy; (13) Significant cardiovascular disease, including any of the following:\n\n 1. New York Heart Association (NYHA) Class II or greater heart failure or left ventricular ejection fraction (LVEF) \\<50% by echocardiography;\n 2. History of clinically significant ventricular arrhythmia (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or arrhythmia requiring continuous antiarrhythmic medication;\n 3. Unstable angina pectoris;\n 4. Myocardial infarction within 12 months;\n 5. Fridericia-corrected QT interval (QTcF) \\>450 msec for males or \\>470 msec for females (if abnormal, three consecutive measurements ≥2 minutes apart, use average);\n 6. Congenital long QT syndrome or family history;\n 7. History of deep vein thrombosis, pulmonary embolism, or other serious thromboembolism within 3 months prior to randomization (implanted port or catheter-related thrombosis, or superficial venous thrombosis not considered "serious");\n 8. Current use or recent use (within 7 days prior to study treatment) of aspirin (\\>325 mg/day), dipyridamole, ticlopidine, clopidogrel, or cilostazol; (14) Active or uncontrolled severe infection (≥CTCAE Grade 2); (15) Renal failure requiring hemodialysis or peritoneal dialysis; (16) History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency disorders; (17) Use of immunosuppressants or systemic or absorbable topical corticosteroids for immunosuppressive purposes within 7 days prior to first dose (except prednisone ≤10 mg daily or equivalent); (18) Epilepsy requiring treatment; (19) Tumor-related symptoms and treatment:\n\n <!-- -->\n\n 1. Cytotoxic chemotherapy, immunotherapy within 3 weeks, or radiotherapy or small molecule targeted therapy within 2 weeks prior to first dose, or within 5 half-lives of drug (whichever is shorter) from last treatment; (prior radiotherapy: target lesions should not be within radiation field, or if within field, progression must be confirmed);\n 2. Traditional Chinese medicines with anti-tumor indications approved by NMPA within 2 weeks prior to first dose (including Compound Cantharis Capsules, Kang\'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Brucea Javanica Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules, etc.);\n 3. Imaging evidence of significant tumor invasion into adjacent organs (aorta or trachea) with increased risk of bleeding or fistula; ulcerative ESCC with increased bleeding risk due to proximity to vessels;\n 4. Known complete esophageal obstruction requiring interventional relief;\n 5. Post-esophageal or tracheal stent placement;\n 6. Uncontrolled pleural effusion, pericardial effusion, or moderate to severe ascites requiring repeated drainage (investigator judgment);\n 7. Known spinal cord compression, carcinomatous meningitis, or brain metastasis with symptoms or symptom control \\<4 weeks; (20) Known hypersensitivity to study drug excipients; (21) Prior treatment with anlotinib hydrochloride or other anti-angiogenic agents, or any anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody; (22) Participation in other interventional clinical trials with investigational drug use within 4 weeks prior to first dose; (23) Pregnancy, lactation, or planned pregnancy during study period; (24) Any condition that, in the opinion of the investigator, would pose significant safety risk to the subject or interfere with completion of the study.'}, 'identificationModule': {'nctId': 'NCT07446335', 'briefTitle': 'A Phase III Study of First-line Anlotinib Combined With Benmelstobart in Patients With Advanced Esophageal Squamous Cell Carcinoma', 'organization': {'class': 'OTHER', 'fullName': 'The First Affiliated Hospital of Zhengzhou University'}, 'officialTitle': 'A Randomized, Open-Label, Parallel-Controlled, Multicenter Phase III Clinical Trial to Evaluate the Safety and Efficacy of Anlotinib Hydrochloride Combined With Benmelstobart Versus Toripalimab Combined With Chemotherapy as First-Line Treatment for Advanced Esophageal Squamous Cell Carcinoma Harboring Specific Gene Mutations', 'orgStudyIdInfo': {'id': 'TQB2450-ALTN-Ⅲ-03'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Anlotinib Hydrochloride Combined with Benmelstobart', 'interventionNames': ['Drug: anlotinib combined with benmelstobart']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Toripalimab in Combination with Chemotherapy', 'interventionNames': ['Drug: Toripalimab Combined with Chemotherapy']}], 'interventions': [{'name': 'anlotinib combined with benmelstobart', 'type': 'DRUG', 'description': 'Benmelstobart injection 1200 mg will be diluted in 250 mL normal saline (0.9% sodium chloride) and administered via intravenous infusion over 60 ± 10 minutes on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or a maximum of 24 months.\n\nAnlotinib hydrochloride capsules 12 mg will be administered orally once daily before breakfast at approximately the same time each day on a schedule of 2 weeks on and 1 week off in 21-day cycles until disease progression or unacceptable toxicity.', 'armGroupLabels': ['Anlotinib Hydrochloride Combined with Benmelstobart']}, {'name': 'Toripalimab Combined with Chemotherapy', 'type': 'DRUG', 'description': 'Induction Phase (maximum 6 cycles):Toripalimab injection 240 mg will be administered intravenously over 60 minutes on Day 1 of each 21-day cycle after dilution in 100 mL normal saline (0.9% sodium chloride). Chemotherapy regimen will be determined prior to randomization based on individual patient characteristics. Patients will receive one of the following chemotherapy regimens per local treatment standards: Cisplatin 60-75 mg/m² intravenously on Day 1 plus paclitaxel 150-175 mg/m² intravenously over \\>3 hours, both administered every 3 weeks; or cisplatin 60-75 mg/m² intravenously on Day 1 plus fluorouracil 700-850 mg/m² daily by continuous intravenous infusion over 24 hours on Days 1-5, repeated every 3 weeks.\n\nMaintenance Phase :Toripalimab injection 240 mg will be administered intravenously over 60 minutes on Day 1 of each 21-day cycle after dilution in 100 mL normal saline (0.9% sodium chloride).', 'armGroupLabels': ['Toripalimab in Combination with Chemotherapy']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Zhengzhou', 'state': 'Henan', 'country': 'China', 'facility': 'The First Affiliated Hospital of Zhengzhou University', 'geoPoint': {'lat': 34.75778, 'lon': 113.64861}}], 'centralContacts': [{'name': 'feng wang', 'role': 'CONTACT', 'email': 'fengw010@163.com', 'phone': '0086-13938244776'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The First Affiliated Hospital of Zhengzhou University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'professor', 'investigatorFullName': 'Feng Wang', 'investigatorAffiliation': 'The First Affiliated Hospital of Zhengzhou University'}}}}