Esophageal Squamous Cell Carcinoma
Conditions
Interventions
Experimental group:Tofacitinib 5mg twice daily for two cycles, combined with apalolide and tovolrelli 5mg/kg once every three weeks until disease progression or 2 years have passed
Sponsors
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects voluntarily join this study, sign the informed consent form, have good compliance, and cooperate with follow-up; 2. Patients with histopathologically confirmed recurrent or metastatic esophageal squamous cell carcinoma; 3. Disease progression after at least two cycles of PD-(L)1 inhibitor ± first-line treatment; 4. Patients with untreated brain metastases; 5. RECIST V1.1 measurable lesions can be biopsied; 6. Age 18-75 years old; 7. ECOG score of 0-1 points; 8. The function of vital organs meets the following requirements (excluding the use of any blood components and cell growth factors during the screening period): absolute neutrophil count >=1.5×10^9/L; Platelets>=100×10^9/L; Hemoglobin>=9g/dL; Serum albumin>=3g/dL; Thyroid-stimulating hormone (TSH) =60mL/min; 9. Non-surgically sterilized or female patients of childbearing age who need to use one medically approved contraceptive measure (such as intrauterine device, birth control pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Non-surgically sterilized female patients of childbearing age must have a negative serum or urine HCG test within 72 hours before study enrollment; and must be non-lactating; For men, use an appropriate method of contraception during the trial and for 3 months after the last dose of the trial drug.
Exclusion criteria
Exclusion criteria: 1. Subjects have used JAK inhibitors in the past; 2. Subjects have any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subject has vitiligo; Asthma that has been completely resolved in childhood and does not require any intervention in adulthood can be included, such as asthma requiring bronchodilators for medical intervention cannot be included); 3. Subjects are using immunosuppressants, or systemic, or absorbable topical hormone therapy for immunosuppressive purposes (dose > 10mg/day prednisone or other equivalent efficacy hormones), and continue to use them within 2 weeks before enrollment; 4. Severe allergic reactions to other monoclonal antibodies or investigational drugs; 5. Have uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA grade 2 or above heart failure; (2) Unstable angina; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTc>450ms (male); QTc>470ms (female); 6. Patients at risk of major bleeding: abnormal coagulation function (INR>1.5 or PT>16s), bleeding tendency, or receiving thrombolytic or anticoagulant therapy; Known hereditary or acquired bleeding and thrombophilia (such as hemophilia patients, coagulopathy, thrombocytopenia, hypersplenism, etc.) or hyperarterial or venous thrombotic events in the past 6 months; 7. Subjects have active infection or unexplained fever >38.5 degrees during screening and before the first dose; 8. Patients with previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonitis, severe impairment of lung function, etc.; 9. Subjects with congenital or acquired immunodeficiency (such as HIV infection), or active hepatitis (hepatitis B reference: HBV DNA test value exceeds the upper limit of normal value; Hepatitis C reference: HCV virus titer or RNA detection value exceeds the upper limit of normal value); 10. Subjects who have used other investigational drugs within 4 weeks before the first dose of the study medication; 11. Subjects with a history of or concurrent other malignancies; 12. Subjects who may receive other anti-tumor treatments during the study; 13. Subjects who have received live vaccines less than 4 weeks before the study medication or may receive them during the study; 14. According to the investigator's judgment, subjects have other factors that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring concomitant treatment, significant laboratory abnormalities, or family or social factors that may affect the subject's safety or the collection of data and samples.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate at 12 weeks;Safety (incidence and severity of adverse events, clinically significant abnormal laboratory findings);duration of response; | — |
Secondary
| Measure | Time frame |
|---|---|
| progression-free survival;overall survival; | — |
Countries
China
Contacts
Public ContactFeng Hong
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Outcome results
None listed