SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.

Korábbi kezelés

• Patients with prior systemic chemotherapy as part of first - or second-line systemic therapy;
• Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, and major surgery were used within 4 weeks before the first dose, and palliative radiotherapy, targeted therapy (including small molecule tyrosine kinase inhibitors), and other anti-tumor treatments were used within 2 weeks before the first dose.
• The cumulative dose of anthracyclines in previous (new) adjuvant therapy was > 360 mg/m\^2;
• Received other unmarketed investigational drugs or treatments within 4 weeks before study enrollment;

Más betegség

• The history of severe heart disease within the past six months was screened, such as symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc.
• Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis);
• Other malignant tumors diagnosed within 5 years before the first dose of treatment, except those with radical basal cell carcinoma, squamous cell carcinoma of the skin, and/or radical resection in situ carcinoma considered by investigators to be eligible;
• Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg);
• Pulmonary disease grade ≥3 was defined according to CTCAE v5.0, including dyspnea at rest, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD).
• Patients with a history of allergy to the recombinant humanized or human-mouse chimeric antibody or to SI-B001 or any of the excipients of the chemotherapeutic agents used in this trial;
• A history of autologous or allogeneic stem cell transplantation;
• Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 10\^4) or hepatitis C virus infection (HCV-RNA > the lower limit of detection in the research center);
• Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc.;
• Other conditions for trial participation were not considered by the investigator to be appropriate

Laborértékek

• Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, atrioventricular block III degree;

Egyéb

• Gene sequencing showed that there were MET, ALK, RET, HER2 and other driver gene mutations related to the occurrence and development of tumors.
• There were symptoms of active central nervous system metastasis. However, patients with stable parenchymal metastases could be enrolled, and whether they were stable was defined by the investigators.

• Voluntarily sign the informed consent and follow the requirements of the protocol;
• Male or female;
• Age: ≥ 18 years;
• Expected survival time ≥ 3 months;
• Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed by histopathology and/or cytology, T790M-negative, Exon20ins mutation resistant to the third generation EGFR TKI after the first or second line treatment, or resistance to the first or second generation TKI after the first line treatment;
• Consent to provide an archived tumor tissue specimen or fresh tissue sample (an FFPE block or approximately 6-12 white slides with a size of 5μm) from the primary or metastatic tumor within 6 months of the date of consent. Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and exclusion criteria after evaluation by investigators.
• Must have at least one measurable lesion as defined by RECISTv1.1;
• Performance status score ECOG0 or 1;
• Toxicity from previous antineochemical therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy).
• No severe cardiac dysfunction, left ventricular score ≥ 50%;
• The level of organ function must meet the following criteria:
  • Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count ≥ 80 × 10\^9/L, hemoglobin ≥ 90 g/L;
  • Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases;
  • Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula).
• Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;
• Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine);
• Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment.