advanced bone and soft tissue sarcoma
Conditions
Interventions
Cohort 1:SHR-1701+Famitinib
Cohort 2:Camrelizumab+SHR-6390
Cohort 3:SHR-2554
Sponsors
Affiliated Sixth People's Hospital, Shanghai Jiaotong University
Eligibility
Sex/Gender
All
Age
14 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged >=12 years, both male and female; 2. ECOG score 0-1 points; 3. Unresectable locally advanced or metastatic osteosarcoma or soft tissue sarcoma confirmed by histopathology; 4. Patients who have failed previous first-line treatment, including patients who have progressed during or within 6 months after receiving neoadjuvant or adjuvant treatment; 5. With different gene or molecular expression: cohort 1, MSI-H/dMMR or TMB> 5 or PD-L1 >= 1%; cohort 2, CDK4 or CDK6 amplification; cohort 3, SMARCB1 (INI1) deletion or EZH2 gene mRNA level is high; (undifferentiated pleomorphic sarcoma and alveolar soft tissue sarcoma can be included in cohort 1 without genetic testing, and highly differentiated or dedifferentiated liposarcoma can be included in cohort 2 without genetic testing) 6. According to the solid tumor remission evaluation criteria (RECIST 1.1), there is at least one measurable lesion; 7. Expected survival period >= 3 months; 8. The main organ function and bone marrow function are normal and meet the following requirements: (1) Hemoglobin >=90 g/L; (no blood transfusion within 14 days) (2) The absolute count of neutrophils>=1.5x10^9/L; (3) Platelet count >=90x10^9/L; (4) Total bilirubin =50%; QTc male <450ms, female <470ms; 9. The international normalized ratio of prothrombin time (INR) <= 1.5, partial thromboplastin time (APTT) <= 1.5 times ULN in patients who have not received anticoagulant therapy. For patients receiving full-dose or parenteral anticoagulant treatment, as long as the anticoagulant dose is stable for at least 2 weeks before entering the clinical study, and the results of the coagulation test are within the limits of local treatment; 10. Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 3 months after the last administration of the study drug; for men, it should be Surgical sterilization or consent to use appropriate methods of contraception during the observation period and within 3 months after the last administration of the study drug; 11. Recovery from previous treatment: According to NCI-CTC AE version 5.0, the toxicity of the previous treatment has been restored to =1 level (if there is surgery, the wound has completely healed); 12. The patient voluntarily participates and signs the informed consent form (or signed by the legal representative). It is expected to have good compliance and be able to cooperate with the research according to the requirements of the plan.
Exclusion criteria
Exclusion criteria: 1. Previously received EZH2 inhibitors (such as Tazemetostat), or CDK4/6 inhibitors (such as piperacillil), or anti-angiogenesis small molecule TKI drugs (such as pezopanib, anlotinib), or I have used anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies and other immune preparations. 2. Have received the following treatments or drugs before the first study treatment: (1) Major surgery has been performed within 28 days before the first study drug treatment (tissue biopsy required for diagnosis is allowed); (2) Vaccine live attenuated vaccine within 28 days before the first study drug treatment or planned during the study period and 60 days after the end of the study drug treatment; (3) Any form of anti-tumor therapy, including radiotherapy, chemotherapy, molecular targeted therapy, and immunotherapy, has been performed within 4 weeks before the first study drug treatment, or participated in another interventional clinical trial; those receiving anti-tumor drug treatment For patients, it is not more than 4 weeks or 5 half-lives of the drug from the last medication; 3. There is a third space effusion (such as a large amount of pleural fluid or ascites) that has clinical symptoms and cannot be controlled by drainage or other methods; 4. Even after drug treatment, hypertension is still poorly controlled (continuous increase in systolic blood pressure >=150mmHg or diastolic blood pressure >=100mmHg) 5. Suffer from any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism; need for bronchus Patients undergoing medical intervention with dilators; 6. Severe infections (such as intravenous infusion of antibiotics, antifungal or antiviral drugs required) within 2 weeks before the first administration, or unexplained fever > 38.5 degree C during the screening period/before the first administration; 7. Arterial/venous thrombosis events that occurred within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.; 8. Suffered from or accompanied by other systemic malignant tumors in the last 5 years, (except for cured skin basal cell carcinoma, cervical carcinoma in situ and ovarian cancer); 9. Those who are known to be allergic to any test drug or its excipients; 10. Have a clear history of neurological or mental disorders, including epilepsy and dementia; 11. Known uncontrollable or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth; 12. Patients who are unable to swallow study drugs, such as chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction and other factors that affect drug administration and absorption; 13. Other situations that the researcher thinks are not suitable for inclusion. If accompanied by family or social factors, it will affect the safety of subjects or the collection of data and samples.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival rate at 12 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Overall survival;Clinical benefit rate;Safety; | — |
Countries
China
Contacts
Public ContactHu Haiyan
The Affiliated Sixth People's Hospital, Shanghai Jiaotong University
Outcome results
None listed