HER2-positive advanced solid tumors
Conditions
Interventions
Experimental group:Inject recombinant anti-HER2/CD3 humanized bispecific antibody(BC004)
Sponsors
Fudan university shanghai cancer center
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1) Voluntarily sign the informed consent form, understand the study and are willing to follow and able to complete all experimental procedures; 2) Male or female subjects aged =18 and =70 years; 3) Dose escalation phase/Security expansion phase:Patients with histologically or cytologically confirmed HER2-positive advanced solid tumors, existing standard regimens failed or not tolerated, or no standard therapy is available, or the subject is considered medically unsuitable for standard therapy by the investigator; Clinical expansion phase: Patients with histologically or cytologically confirmed HER2-positive advanced breast cancer or HER2-positive advanced gastric cancer/gastroesophageal junction adenocarcinoma or other HER2-positive advanced solid tumors (including but not limited to urothelial cancer, biliary tract cancer, non-small cell lung cancer, gynecological tumors, etc.), or other advanced solid tumors with low HER2 expression; no standard therapy, or intolerant to standard therapy, or treatment failure, or the investigator considers the subject unsuitable for standard therapy due to medical considerations; 4) Dose escalation phase/Security expansion phase:those whose previous HER2 expression status report showed positive, or the tumor tissue biopsy in the local laboratory during the screening period was positive for HER2 expression status; Clinical expansion phase: those whose previous HER2 expression status report showed positive or low expression, or those with positive or low expression of HER2 in the local laboratory on tumor tissue biopsy during the screening period. Note: HER2 positivity is defined as: IHC 3+ by immunohistochemistry, or IHC 2+ by immunohistochemistry and ISH positive (breast cancer ISH positive: total HER2 signals/total CEP17 signals =2.0 or total HER2 signals/total CEP17 signals <2.0 and average HER2 copy number/cell =6.0; gastric cancer ISH positive: HER2 signal number/tootal CEP17 signals=2.0); low HER2 expression is defined as: immunohistochemical IHC 1+ or immunohistochemical IHC 2+ and ISH negative; it is recommended to collect the proportion of HER2 positive cells in patients with gastric cancer; according to the disease and treatment history, those whose HER2 expression status may change (such as after anti HER2 treatment) should be re-examined during the screening period as much as possible; 5) According to the RECIST v1.1, there should be at least one target lesion measurable by imaging (the target lesion has not received radiotherapy before, and the same subject should try to use the same detection method, CT or MRI,CT or MRI contraindications such as dentures, joint replacements should be paid attention); 6) Dose escalation phase: patients with ECOG score =1; Security expansion phase/Clinical expansion phase: patients with ECOG score =2; 7) Expected survival period =12 weeks; 8) LVEF =50% at rest; 9) Male subjects and their spouses and female subjects of childbearing age should agree to take effective contraceptive measures from signing the informed consent form until 6 months after the last dose.
Exclusion criteria
Exclusion criteria: 1) Patients with symptomatic CNS metastases; 2) Allergy to the components or excipients of the test drug, monoclonal antibodies, or any other therapeutic proteins (such as fresh frozen plasma, human serum albumin (HSA), cytokines or interleukins, etc.); or have a history of severe allergies, suspected severe allergic reactions may occur (CTCAE v5.0 =3); 3) Within 28 days or 5 half-lives before the first dose of this study (depending on the elderly, the oral fluorouracil should be at least 14 days away from the last dose, and the mitomycin C and nitrosoureas should be at least 6 weeks away from the last dose), the patient has received any chemotherapy drugs, other clinical trial drugs or anti-tumor drugs and radiotherapy; 4) Known uncontrolled active bacterial, viral, fungal, mycobacterial, parasitic, or other infections (excluding nail bed dermatophyte infection) within 4 weeks prior to enrollment or any major systemic infection event requiring intravenous antibiotic treatment or hospitalization (except neoplastic fever); 5) Those who have been vaccinated within 4 weeks before screening; 6) Patients with autoimmune diseases [such as the following, but not limited to: uveitis, enteritis, hepatitis, etc. (except radiotherapy); subjects with vitiligo or asthma in childhood who have been completely relieved and do not need any intervention after adulthood can be included; subjects requiring bronchodilator medical intervention for asthma cannot be included] whose treatment time =6 months (long-term use of any dose of immunosuppressants or glucocorticoids, etc.); 7) Patients with acute lung disease, interstitial lung disease or pneumonia, pulmonary fibrosis, etc., or other serious respiratory diseases, the investigator judges that they are not suitable to participate in this trial; 8) 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 cancer, or any type of carcinoma in situ that has been completely removed, such as cervix in situ, breast ductal carcinoma in situ, etc.); 9) History of serious cardiovascular disease, including patients who have received coronary artery bypass grafting or coronary stenting in the past, myocardial infarction within 6 months, history of congestive heart failure or unstable angina pectoris, uncontrolled severe hypertension (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg) and arrhythmias requiring drug therapy; 10) The cardiac function class (NYHA) is class III or IV; 11) Uncontrolled metabolic diseases such as diabetes, severe gastrointestinal bleeding (CTCAE=2), severe diarrhea (CTCAE=2), severe gastrointestinal obstruction (CTCAE=3) requiring intervention; 12) The laboratory test value of the subject is within the following range: a. Absolute neutrophil count (ANC) 1.5×ULN; e. Aspartate aminotransferase (AST) and glutamate aminotransferase (ALT) >2.0×ULN, or when the investigator judges that they are elevated due to tumor liver metastasis, ALT and AST >5.0×ULN; f. Serum total bilirubin (TBIL) >1.5×ULN; g. International normalized ratio (INR) >2×ULN, or activated partial thromboplastin time (APPT) >1.5×ULN; 13) Known infection of at least one of human immunodeficiency virus (HIV), hepatitis B virus (both HBsAg positive and HBV-DNA copy number p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-related adverse events during and within 30 days of treatment; | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the pharmacokinetic parameters of multiple doses of BC004 in patients with HER 2 positive advanced solid tumors;;To evaluate the pharmacodynamic parameters of single / multiple administration of injected BC004 in patients with HER 2 positive advanced solid tumors;To assess the incidence and antibody titers of anti-drug antibodies and neutralizing antibodies to BC004 for injection in patients with advanced solid tumors positive for HER 2;Overall response rate (Overall Response Rate, ORR): defined as complete response (Complete Response, CR) and partial response (Partial in the RECISTv1.1 evaluable population Response, PR), the proportion of cases in the total number of cases;;Optimal response rate (Best Overall Response Rate, BOR): defined as the proportion of cases in the treatment of the RECIST v1.1 evaluable population;;Disease control rate (Disease Control Rate, DCR): defined as the proportion of cases in total cases with complete response (CR), partial response (PR) and stable disease (StableDisease, SD) in the RECIST v1.1 evaluable population after treatment;;Persistent response (Duration of Response, DoR): defined as the interval between the RECIST v1.1 evaluable population from the first assessment of CR or PR to the first assessment of the disease progression (Progression Disease, PD) or death from any cause;;Progression-free survival (Progression Free Survival, PFS): defined as the interval from the first dose to disease progression or death from any cause;;Time to disease stabilization (Duration of SD): defined as the time from the first dose to the first assessment as SD;;Time to remission (Time to response, TTR); defined as time from the first dose to the first assessment as CR or PR;;Duration of treatment (Time on therapy): defined as the time from the first dose to the last dose.; | — |
Countries
China
Contacts
Public Contactzhangjian
Fudan university shanghai cancer center
Outcome results
None listed