Advanced malignant tumor
Conditions
Interventions
Experimental group:Intravenous injection of BR105
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Those who voluntarily sign informed consent, understand the nature, purpose and procedure of the experiment and can complete the experiment according to the scheme; 2. Aged 18-75 years (patient to the date of signing the informed consent), gender unlimited; 3. Stage Ia: patients with advanced malignant tumors or relapsed refractory malignant lymphoma who have been confirmed by histopathology or cytology and have failed standard treatment or are intolerant or have no standard effective treatment options; Phase Ib: The Phase Ib dose expansion study will be limited to specific patients based on the results of the Phase Ia trial, which will initially include patients with relapsed refractory B-cell non-Hodgkin lymphoma and patients with advanced gastric cancer; 4. Physical state score of Eastern Tumor Collaboration Group (ECOG) =3 months; 6. According to the RECIST v1.1 or Lugano 2014 criteria, patients with stage Ia may have no measurable lesion at baseline, and patients with stage Ib may have at least one measurable lesion at baseline (bone metastases only or central nervous system (CNS) only metastases are not accepted as measurable lesions); 7. Patients who have received antitumor therapy in the past should not be enrolled until toxicity from previous therapy has returned to CTCAE v5.0 score = 1,500/mm^3 (1.5x10^9/L); (2) Platelet count (PLT) >=100,000/mm^3 (100x10^9/L); (3) Hemoglobin (HGB) >=9g/dL (90g/L); (4) Serum creatinine (Cr) = 50 ml/min; (5) Total bilirubin (TBIL) <=1.5xULN, patients with liver metastasis or liver cancer <=2xULN; (6) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level <=2.5xULN, patients with liver metastasis or liver cancer should be <=5xULN; (7) International Standardized ratio (INR) <=1.5, prothrombin time (PT) and activated partial thrombin time (APTT) <=1.5xULN; 9. The serum pregnancy test results of female patients of childbearing age must be negative at the time of admission to this study; Female patients of childbearing age or male patients with a female sexual partner of childbearing age were willing to use appropriate and effective contraceptive methods such as abstinence and double barrier (e.g., condom and diaphragm), oral contraceptives, and IUD placement during the study period and for 6 months after the last test drug administration.
Exclusion criteria
Exclusion criteria: 1. Known allergy to the test drug or any of its excipients; Or have had a severe allergic reaction to other monoclonal antibodies; 2. Previous therapy with targeted anti-CD47 or anti-SIRPa drugs; 3. A history of hemolytic anemia (including Evans syndrome) or autoimmune thrombocytopenia from any cause within 3 months prior to initial administration of the investigatory drug; 4. Patients who are receiving thrombolytic or anticoagulant therapy due to high risk of thrombosis; 5. Received the following treatments or medications before the initial study treatment: (1) Major surgery was performed within 28 days prior to treatment with the initial investigational drug, or major surgery is expected to be performed during the study period (tissue biopsies required for diagnosis are permitted); (2) Use of immunosuppressive drugs within 14 days before treatment with the first experimental drug; In the absence of active autoimmune disease, intranasal and inhaled corticosteroids or systemic steroid hormones at physiological doses are permitted (i.e., no more than 10 mg/ day of prednisone or equivalent drug physiological doses of other corticosteroids); (3) Live attenuated vaccine received within 28 days before treatment with the first investigational drug or planned during the study period and within 60 days after the end of treatment with the investigational drug; (4) Receiving antitumor therapy (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biotherapy or tumor embolization) within 28 days prior to treatment with the first investigational drug; Or use of therapeutic radiation within 56 days prior to treatment with the first experimental drug; (5) Those who have participated in other clinical trials and used trial-related drugs within 28 days prior to the first investigational drug treatment; 6. A history of active or potentially recurrent autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc. Except for those with only alternative treatment (e.g., residual hypothyroidism due to autoimmune thyroiditis); 7. Patients with central nervous system metastases, uncontrollable pleural effusion, pericardial effusion or abdominal effusion (except patients with indwelling catheter); Or uncontrolled hypercalcemia; Or combined with spinal cord compression; 8. Any other malignancies within the previous 2 years, excluding completely cured cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin, other previously treated malignancies that the investigator determined to be stable at present, and other malignancies that the investigator determined might benefit from the study; 9. Positive for human immunodeficiency virus (HIV) antibodies; Treponema pallidum (TP) antibody positive; Hepatitis C virus (HCV) antibody positive, and HCV RNA quantitative detection results greater than the lower limit of detection; Hepatitis B surface antigen (HBsAg) positive or Hepatitis B core antibody (HBcAb) positive, and hepatitis B virus DNA detection result >=1 10^3IU/ml; 10. There are serious poorly controlled concomitant diseases, such as: congestive heart failure (NYHA Grade II or higher), arrhythmia or angina with increased thromboembolic events, coronary stenting, angioplasty, or coronary artery bypass grafting within the last 6 months, treatment of uncontrolled hypertension (systolic bloo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerance;Safety;Antitumor activity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of pharmacokinetics;Evaluation of immunogenicity;Evaluation of antitumor activity; | — |
Countries
China
Contacts
Public ContactZhu Jun
Outcome results
None listed