Non small cell lung cancer
Conditions
Interventions
Single arm group:Distamab Vedotin plus Anlotinib
Sponsors
Jiangsu Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Patients are able to understand the informed consent form, are willing to join in this study and have signed the informed consent. 2.Aged >= 18 years when signing the ICF, and no limitation of gender. 3.Metastatic or locally advanced unresectable NSCLC confirmed by histology or cytology. 4.Harboring HER2 variants, which are defined (satisfying any of the following) as: HER2 mutation (RT-PCR or NGS),HER2 amplification (FISH+ : HER2/CEP17 ratio =2 or NGS),HER2 overexpression (IHC 3+ or 2+). 5.Experience first-line or standard treatment failure (disease progression after treatment or intolerance of toxic and side effects of treatment). 6.ECOG PS 0 or 1. 7.At least one untreated lesion measurable by the investigator according to RECIST v1.1. 8.Adequate heart, bone marrow, liver, and kidney function should meet the following criteria within 7 days prior to study administration:Left ventricular ejection fraction =50%; Hemoglobin =9 g/dL; Absolute neutrophil count (ANC) =1.5×10^9/L; Platelets = 100 × 10 ^ 9/L; Serum total bilirubin = 1.5 times the upper limit of normal value (ULN); In the absence of liver metastasis, ALT and AST=2.5×ULN, in the presence of liver metastasis, ALT and AST=5×ULN;Serum creatinine =1.5×ULN or creatinine clearance (CrCl) =50 mL/min; Coagulation function: activated partial thromboplastin time (APTT), International Normalized ratio (INR), prothrombin time (PT) = 1.5×ULN. 9.Expected survival period >= 3 months. 10.Women of reproductive age should agree to use contraceptives (such as intrauterine devices [IUD], birth control pills or condoms) during the study period and for 6 months after the study ends; Have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be a non-lactating patient; Men should consent to patients who must use contraception during the study period and for 6 months after the end of the study period; 11. The subject is able and willing to comply with visits, treatment plans, laboratory tests, and other study-related procedures as specified in the study protocol.
Exclusion criteria
Exclusion criteria: 1.Patients who have previously received anti-HER2 antibody or ADC drugs. 2.Previously received small-molecule antiangiogenic drugs, not limited Anlotinib, Apatinib, etc. 3.Patients who are allergic to the RC48 or androtinib. 4.Antitumor therapy, including chemotherapy, radiotherapy (palliative radiotherapy for bone metastases > 2 weeks before baseline detection of tumors is acceptable), targeted therapy, immunotherapy and clinical antitumor drug therapy, were received within 3 weeks before the start of the study. 5.Have central nervous system metastases and/or cancerous meningitis. Participants who have previously received BMS may be considered for participation in this study if their disease has been stable for at least 3 months, imaging has determined that no disease progression has occurred during the 4 weeks prior to the first dosing of the study, all neurological symptoms have returned to baseline, and there is no evidence of new or expanded BMS. The use of radiation, surgery, or steroid therapy was discontinued at least 28 days before the first administration of the study treatment. This exception does not include cancerous meningitis, which should be excluded regardless of whether it is clinically stable; 6.Combined disease/medical history 1) Clinically significant hemoptysis (> 50ml daily hemoptysis) occurred within 3 months prior to enrollment; Or clinically significant bleeding symptoms or definite bleeding tendencies, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood or above at baseline, or vasculitis; 2) arteriovenous thrombosis events occurring within 6 months before randomization, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except venous thrombosis caused by intravenous catheterization during previous chemotherapy and cured by researchers) and pulmonary embolism; 3) hypertension that is not well controlled by antihypertensive medications (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg); In the 6 months prior to randomization, the following conditions had occurred: myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or higher cardiac dysfunction, clinically significant supracentricular or ventricular arrhythmias, and symptomatic congestive heart failure; 4) Renal insufficiency: urine routine suggests urinary protein = ++, or confirmed 24-hour urinary protein volume =1.0g; 5) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); Active hepatitis (Hepatitis B, defined as HBV-DNA = 500 IU/ml; Hepatitis C, defined as HCV-RNA above the lower detection limit of analytical methods) or co-infection with hepatitis B and hepatitis C; 6) Severe infection, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc. within 4 weeks before the first dose; Active infection of CTCAE grade =2 requiring systemic antibiotic treatment within 2 weeks prior to first administration, or unexplained fever >38.5°C during screening/prior to first administration (fever due to tumor, as determined by the investigator, was eligible for inclusion); Evidence of active tuberculosis infection within 1 year prior to administration; 7) Major surgery within 28 days prior to initial dosing (tissue biopsy required for diagnosis and peripherally inserted central venous catheter operation [PICC] or infusion PORT (PORT) permitted); 8) Subjects who have previously received o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose;Phase II recommended dose;Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate;Progression-free survival;Duration of disease remission;Overall survival;Safety; | — |
Countries
China
Contacts
Public ContactShen Bo
Jiangsu Cancer Hospital
Outcome results
None listed