Advanced solid tumor
Conditions
Interventions
dose escalation:BC001
dose escalation:BC001+paclitaxel
dose expansion:BC001
dose expansion:BC001+paclitaxel
dose expansion:BC001+chemotherapy
dose expansion:BC001+PD-1/PD-L1
Sponsors
Beijing University Cancer Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be able to understand and voluntarily sign written informed consent. Informed consent includes dose escalation, research expansion phase, and relevant requirements for sample collection in the two-phase study; 2. Subjects must be voluntary and able to complete the research procedures and follow-up examinations; 3. Male or female subjects aged >= 18 years; 4. Dose escalation phase: subjects with advanced malignant solid tumors confirmed by histopathology or cytopathology, mainly including but not limited to: gastric cancer and gastroesophageal junction adenocarcinoma, non-small cell lung cancer, metastatic colorectal cancer, Melanoma, renal cell carcinoma, bladder urothelial carcinoma, osteosarcoma, neuroendocrine tumor, etc.; Research expansion Phase: Subjects with advanced malignant solid tumors confirmed by histopathology or cytopathology, including but not limited to: gastric cancer and gastroesophageal junction adenocarcinoma, non-small cell lung cancer, metastatic colorectal cancer, melanoma Tumor, renal cell carcinoma, bladder urothelial carcinoma, osteosarcoma, neuroendocrine tumor, etc., according to RECIST version 1.1 to determine at least one measurable tumor lesion shown by CT or MRI; *Measurable lesions are defined as >= 10 mm in longest diameter and no more than 5.0 mm in scan thickness. For lymph node lesions, the short diameter is >= 15 mm; 5. In research expansion phase, subjects who have progressed after first-line standard treatment, can not tolerate standard treatment or have no standard treatment are enrolled; 6. The ECOG score is 0-1; 7. The estimated life expectancy >= 3 months; 8. No serious hematology, liver and kidney function abnormalities, in line with the following laboratory test results: (1) Hematology: neutrophils >= 1.5 x 10^9/L, platelets >= 75 x 10^9/L, hemoglobin >= 90 g/L; (2) Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 50 mL/min; (4) Coagulation function: International normalized ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5 x ULN or activated partial prothrombin time (APTT) <= 1.5 x ULN. Subjects receiving anticoagulant therapy should receive stable doses of oral anticoagulants or low molecular weight heparin. If the subject treated with warfarin, the INR should be <= 3.0 without active bleeding (no bleeding within 14 days prior to the study drug) or clinical conditions with an increased risk of bleeding; (5) Urine routine test urine protein concentration <= 1+, without edema or serum albumin level lower than LLN; 9. Recovery from adverse events of prior anti-tumor therapy to baseline or <= grade 1 (except: alopecia and vitiligo; prior anti-tumor therapy-induced neuropathy stable or <= grade 2); 10. Male or female subjects take effective contraceptive measures during treatment and within 6 months after the last dose.
Exclusion criteria
Exclusion criteria: 1. Received anti-tumor therapy or clinical trials within 4 weeks before enrollment, including systemic chemotherapy, radiotherapy or immunotherapy. Received bevacizumab or other VEGF/VEGFR antibody therapy within 4 weeks before enrollment; 2. Research expansion phase: the subjects in the PD1 treatment group have previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies or other antibodies for T cell co stimulation / checkpoint pathway; 3. Suffering from other malignancies other than the tumors treated in this study (exceptions include: malignancies that are cured and have not recurred within 3 years prior to study enrollment; completely resected basal cell and squamous cell skin cancers; completely resected any type of carcinoma in situ); 4. The original lesion invades the central nervous system (CNS) and is symptomatic, unstable or requires high-dose steroids (>= 10 mg dexamethasone or equivalent dose) to achieve control; 5. Active infections (such as viral, bacterial or fungal infections) requiring systemic treatment; 6. Subjects with a history of active bleeding within the past 4 weeks or a risk of gastrointestinal perforation, recent surgery that has not healed, or a history of wound complications caused by surgical operations; 7. Major surgery within 4 weeks before the first dose of study treatment; 8. Received colony-stimulating factor, erythropoietin and other treatments within 2 weeks before the study drug; 9. Received with live vaccine within 4 weeks before study medication; 10. Subject has uncontrolled episodic disease, including but not limited to: thrombotic or bleeding disorders, hemoptysis, persistent or active infection requiring systemic antibiotic therapy, congestive heart failure (New York Heart Association III or Grade IV heart disease); angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months prior to study medication; stroke, transient ischemic attack (TIA) or other = 6 months prior to study medication Grade 3 arterial thromboembolic event; uncontrolled hypertension (BP >= 150/90 mmHg after standard therapy); arrhythmia requiring treatment (CTCAE v5.0 >= Grade 3) or asymptomatic, sustained ventricular tachycardia; Grade >= 2 (CTCAE v5.0) peripheral neuropathy of any etiology; 11. The subject has experienced >= grade 3 (CTCAE v5.0) gastrointestinal bleeding within 3 months before the study medication; severe gastrointestinal disease within 2 weeks before the study medication; 12. Receiving long-term treatment with non steroidal anti-inflammatory drugs (such as indomethacin, ibuprofen, etc.) or antiplatelet drugs (such as clopidogrel, ticlopidine, dipyridamole, etc.) (aspirin is allowed, with a maximum daily dose of 325mg); 13. Hepatitis B surface antigen positive, and HBV DNA copy number > the normal value of the detection unit; Hepatitis C virus antibody positive and HCV RNA positive; 14. History of human immunodeficiency virus infection, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 15. Known allergy to study drugs, monoclonal antibodies and other therapeutic protein preparations (fresh or frozen plasma, human serum albumin, cytokines, interleukins, etc.); 16. Known to be alcohol and/or drug dependent; 17. Positive blood pregnancy test or female subjects who are breastfeeding; 18. Subjects who are judged by the investigator to be unsuitable to participate in this study due to other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DLT and incidence of BC001 per dose level in subjects with advanced solid tumors (Dose escalation phase);DLT and incidence of BC001 per dose level used in combination with paclitaxel in subjects with advanced solid tumors (Dose escalation phase);The safety of BC001 in Chinese subjects with advanced solid tumors was assessed by post-treatment adverse events, blood routine, blood chemistry and urine routine laboratory tests, physical examination, vital signs, and electrocardiogram (Dose-escalation phase);Determine the efficacy of BC001 alone and in combination with chemotherapy or immunotherapy, including: objective overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival time (PFS) (Study Extension Phase); | — |
Secondary
| Measure | Time frame |
|---|---|
| In subjects with advanced solid tumors, BC001 pharmacokinetic parameters (Dose-escalation phase);In subjects with solid tumours, the effectiveness of BC001 monotherapy and BC001 combined with paclitaxel was initially evaluated, including: objective overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) (Dose-escalation phase);The safety of BC001 alone and in combination with chemotherapy or immunotherapy in subjects with protocol specified tumors was evaluated by safety measures, including post-treatment adverse events, blood routine, blood chemistry and urine tests, physical examination, vital signs, and electrocardiogram (Study Extension Phase); | — |
Countries
China
Contacts
Public ContactShen Lin
Beijing University Cancer Hospital
Outcome results
None listed