Advanced solid tumor
Conditions
Interventions
Experimental group:BC008-1A for injection
Sponsors
Cancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. (1) Dose increasing stage: locally advanced, relapsed or metastatic solid tumors that have failed standard therapy or have no effective standard therapy, or are intolerant to standard therapy. Standard treatment failure refers to that subjects have received standard treatment based on the agreed standard treatment guidelines in China (if any) or based on the current domestic treatment status, and disease progression or tumor recurrence and metastasis occurs during or after treatment; (2) Study extension: non-small cell lung cancer, colorectal cancer, gastric cancer and other advanced solid tumors (esophageal cancer, nasopharyngeal cancer, etc.) confirmed by histology or cytology; 2. Sign a written informed consent prior to any study specific procedures and be able to follow protocol visits and related procedures; 3. No gender limit, aged 18-75 years; 4. Expected survival time >=12 weeks; 5. According to RECIST1.1, there was at least 1 measurable tumor lesion on CT or MRI (no previous radiotherapy). If a lesion located in an irradiated area that received prior radiotherapy clearly demonstrates progression in line with RECIST1.1 criteria, the lesion may be treated as a measurable lesion; 6. The physical state score (ECOG) was 0 or 1 according to the Eastern Oncology Consortium; 7. Adequate blood system function, liver function and kidney function, meeting the following laboratory test results before enrollment: (1) The blood system was basically normal: neutrophil absolute count (ANC) >=1.5x10^9/L, platelet (PLT) >=90x10^9/L, hemoglobin (Hb) >=90g/L; (2) Liver function is basically normal: Total bilirubin (TBIL) =28g/L; (3) Basically normal renal function: creatinine (Cr) =50mL/min (calculated by Cockcroft-Gault formula); (4) The coagulation function is basically normal: International standardized ratio (INR) =50%; 11. Recovery from adverse events of prior antitumor therapy to baseline or <= grade 1 (except: alopecia and vitiligo; Neuropathy induced by previous antitumor therapy is stable or <= grade 2).
Exclusion criteria
Exclusion criteria: 1. Previous exposure to any anti-TIGIT drugs; 2. Participating in another interventional clinical study, except for participating in an observational (non-interventional) clinical study or being in the survival follow-up phase of the interventional study; 3. Received any study drug within 4 weeks prior to the first dose of the study drug; 4. Patients with autoimmune diseases or a history of autoimmune diseases or related symptoms; 5. Four weeks before the first time of study drug administration, or five half-life of the last anti-tumor treatment: systemic chemotherapy (oral fluorouracil drugs washout period for 2 weeks, mitomycin C and nitrosourea drug washout period for 6 weeks), endocrine therapy, targeted therapy (small molecule targeted therapy washout for 2 weeks or five half-life, will be older), immunotherapy, tumor embolization or including anti-tumor indications for Chinese herbal medicine treatment, etc.; 6. Treatment with corticosteroids or other immunosuppressants within 4 weeks before the first dose of the study drug; 7. Receiving a live attenuated vaccine within 4 weeks or planned during the study prior to the first administration of the study drug; 8. Nonrecovery to NCI-CTCAEv5.0 level 0 or 1 toxicity (excluding alopecia or fatigue) from prior antitumor therapy, including imimmune-relatedAdverseevent (irAE) from immunotherapy, within 4 weeks prior to the first dose of study therapy; 9. A history of pneumonia requiring hormonal therapy, or interstitial lung disease (including past history and current disease history); 10. There are currently active infected persons (such as acute bacterial infection, tuberculosis, active hepatitis B / C, lung infection, etc.); 11. Known central nervous system (CentralNervousSystem, CNS) metastasis and / or spinal cord compression and / or cancerous meningitis, and a history of soft cerebrospinal membrane carcinoma; 12. Positive hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg), and HBV DNA above the upper normal limit of the study center, or doctors judged active hepatitis, hepatitis C virus (HCV) infection, or human immunodeficiency virus (HIV) antibody positive, or treponema pallidum antibody (Tp-Ab) positive; 13. Have clinical cardiac symptoms or diseases that are not well controlled, such as uncontrolled hypertension (systolic blood pressure >=160mmHg and/or diastolic blood pressure >=100mmHg), unstable angina, or myocardial infarction within 6 months prior to enrollment, or poorly controlled arrhythmia (including QTc interval male >=450ms, female >=470ms, QTc interval calculated by Fridericia formula), etc.; 14. Cardiac function classification (NYHA) is grade III or grade IV; 15. With other malignancies within five years (except for completely cured or curable cancers, such as basal skin cancer or squamous cell skin cancer, localized low-risk prostate cancer, papillary thyroid carcinoma, or any type of completely resected carcinoma in situ, such as carcinoma of the cervix, intraductal carcinoma in situ, etc.); 16. Allergy to the components or excipients of the test drug, antibody drugs, or any other therapeutic protein (such as, fresh frozen plasma, human serum albumin, cytokines, or interleukin), or a history of severe allergies, suspected the possibility of severe allergic reactions (NCI-CTCAEv5.0>=3); 17. History of alcohol, drug or drug abuse within 1 year prior to screening; 18. A clear past history of neurological or psychiatric disorders, such as epilepsy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose restriction toxicity (DLT);Maximum tolerated dose (MTD);Adverse events (AE), serious adverse events (SAE);Lab tests, vital signs; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR), disease control rate (DCR);Pharmacokinetic parameters of single / multiple administration of BC008-1A injection;Positive rate of anti-drug antibodies (ADA) and / or neutralizing antibodies (Nab);Receptor occupancy of TIGIT and PD-1 in peripheral blood CD3 +, CD4 +, and CD8 + T cells;Relationship between antitumor efficacy of BC008-1A injection and biomarkers of CD155, TMB, MSI/MMR, PD-L1, peripheral blood T lymphocytes (CD3+, CD4+, CD8+), proliferation index Ki-67, cytokines (IL-2, IL-6, IL-10, TNF-a, IFN-?) in NK cells, PD-1 or Tigit-positive T cell subsets;Progression-free survival (PFS), overall survival (OS);Duration of response (TTR), duration of response (DOR); | — |
Countries
China
Contacts
Public ContactShi Yuankai
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed