A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer

Inclusion criteria

• Voluntary signed informed consent.
• Male or female, Aged between 18 to 75 years.
• Predicted survival ≥ 12 weeks.
• According to UICC/AJCC 8th Edition, histologically and/or cytologically-confirmed, cannot be surgically removed, locally advanced or metastatic NSCLC.
• Locally advanced or metastatic disease had failed at least one systemic treatment.
• Based on imaging judgment (RECIST 1.1) or clinical status, tumor progression during or after the last treatment before enrollment.
• HER2 protein overexpression (IHC 2+ or 3 +) or HER2 gene mutation (defined as exon 20 mutation), the previous test results confirmed by the researchers, both research centers and major research centers can be acceptable.
• The researchers confirmed that the EGFR gene mutation status was negative or positive. For EGFR gene mutation-positive patients, one of the following is met: 1) T790M gene mutation negative, c-Met gene amplification negative and HER2 IHC 2+ or 3+ after first-generation EGFR-TKI drug resistance; 2) Third-generation EGFR-TKI treatment failed and HER2 IHC 2+ or 3+.
• Measurable lesion according to the RECIST 1.1.
• ECOG performance status score of 0 or 1.
• Adequate organ function: LVEF ≥ 50 %. Hemoglobin ≥ 9g/dL; ANC ≥ 1.5×10^9 /L; Platelets ≥ 100×10^9 /L; Total bilirubin ≤ 1.5×ULN; ALT, AST and ALP ≤ 2.5×ULN and ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN, or CrCl ≥ 60mL/min; INR≤ 1.5× ULN, APTT≤ 1.5× ULN.
• For female subjects: should be surgically sterilized, postmenopausal, or agree to use a medically approved contraceptive (such as an intrauterine device, contraceptives, or condoms) during study treatment and within 6 months after the end of study, the blood pregnancy test within 7 days of study enrollment must be negative and must be non-lactating. Male subjects: Patients who should be surgically sterilized or agree to use a medically approved contraceptive during the study treatment period and within 6 months after the end of the study.
• Willing and able to follow trial and follow-up procedures.

Exclusion criteria

• Have used T-DM1 or participated in other HER2-ADC clinical studies.
• Received anti-tumor treatment 4 weeks before study administration, including chemotherapy (late toxicity chemotherapy was 6 weeks before study administration), radiotherapy (palliative local radiotherapy for bone metastases was 2 weeks before the study administration), biological therapy (small molecule targeted drugs were 8 days before the study administration) or immunotherapy, etc.
• Major surgery was performed within 4 weeks prior to study administration and did not fully recover.
• Other clinical trial drugs have been used within 4 weeks before the start of study administration.
• Live vaccine received within 4 weeks before the start of study administration.
• Have received anti-tumor Chinese medicine treatment within 2 weeks before the start of study administration.
• History of other malignant tumors within 5 years before signing the informed consent (except for non-melanoma skin cancer, cervical carcinoma in situ that has been effectively treated, or malignant tumors that have been resolved for more than 3 years after effective treatment and are considered to be cured) .
• Toxicity of previous anti-tumor treatment has not recovered to CTCAE (version 4.03) 0-1, except for the following conditions: a. Hair loss; b. Pigmentation; c. Long-term toxicity caused by radiotherapy, which cannot be restored by the judgement of the investigator.
• Active central nervous system (CNS) metastasis and/or cancerous meningitis (subjects who have received brain metastasis treatment can participate in this study, provided that the condition is stable (no evidence of progression confirmed by imaging studies at least 4 weeks before study dosing, and all neurological symptoms have returned to baseline levels), no evidence of new or enlarged brain metastases, and discontinuation of steroid treatment at least 7 days before the first dose of trial treatment. This exception does not include cancerous meningitis, which should be excluded whether clinical status was stable).
• Diagnosed with HBsAg positive and HBV DNA positive, or HCV Ab positive, or HIV Ab positive.
• Severe arterial/venous thrombosis or cardio-cerebral vascular accidents occurred within 1 year before the study, such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc.
• Active infections requiring systemic treatment.
• Other lung diseases required systemic treatment such as active tuberculosis, interstitial lung disease, etc.
• Uncontrolled systemic diseases such as diabetes, hypertension, cirrhosis, etc.
• Heart failure graded 3 or above by the NYHA.
• Pleural effusion, pericardial effusion, or peritoneal effusion with clinical symptoms that cannot be controlled by drainage or other methods.
• Mental illness or substance abuse known to have an impact on compliance with study requirements.
• Hypersensitivity or delayed allergic reaction to certain components of RC48-ADC or similar drugs.
• Any other disease, metabolic abnormality, abnormal physical examination or abnormal laboratory test, etc., based on the judgment of the investigator, it is reasonable to suspect that the patient has a certain disease or condition unsuitable for the research drug, or will affect the interpretation of the research results, or putting patients at high risk.
• Pregnant or lactating female or female / male who are planning to have children.
• Insufficient adherence to participate in this clinical study.
• Any other condition in which the investigator considers the patient unsuitable for this study.