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

A Phase Ib Study to Evaluate the Efficacy and Safety of RC48-ADC for Injection in Subjects With Advanced Non-small Cell Lung Cancer With HER2 Overexpression or HER2 Mutation

This study will evaluate the efficacy and safety of RC48-ADC for injection in subjects with advanced non-small cell lung cancer with HER2 overexpression or HER2 mutation.

Inclusion Criteria:

1. Voluntary signed informed consent.
2. Male or female, Aged between 18 to 75 years.
3. Predicted survival ≥ 12 weeks.
4. According to UICC/AJCC 8th Edition, histologically and/or cytologically-confirmed, cannot be surgically removed, locally advanced or metastatic NSCLC.
5. Locally advanced or metastatic disease had failed at least one systemic treatment.
6. Based on imaging judgment (RECIST 1.1) or clinical status, tumor progression during or after the last treatment before enrollment.
7. 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.
8. 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+.
9. Measurable lesion according to the RECIST 1.1.
10. ECOG performance status score of 0 or 1.
11. 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.
12. 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.
13. Willing and able to follow trial and follow-up procedures.

Exclusion Criteria:

1. Have used T-DM1 or participated in other HER2-ADC clinical studies.
2. 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.
3. Major surgery was performed within 4 weeks prior to study administration and did not fully recover.
4. Other clinical trial drugs have been used within 4 weeks before the start of study administration.
5. Live vaccine received within 4 weeks before the start of study administration.
6. Have received anti-tumor Chinese medicine treatment within 2 weeks before the start of study administration.
7. 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) .
8. 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.
9. 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).
10. Diagnosed with HBsAg positive and HBV DNA positive, or HCV Ab positive, or HIV Ab positive.
11. 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.
12. Active infections requiring systemic treatment.
13. Other lung diseases required systemic treatment such as active tuberculosis, interstitial lung disease, etc.
14. Uncontrolled systemic diseases such as diabetes, hypertension, cirrhosis, etc.
15. Heart failure graded 3 or above by the NYHA.
16. Pleural effusion, pericardial effusion, or peritoneal effusion with clinical symptoms that cannot be controlled by drainage or other methods.
17. Mental illness or substance abuse known to have an impact on compliance with study requirements.
18. Hypersensitivity or delayed allergic reaction to certain components of RC48-ADC or similar drugs.
19. 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.
20. Pregnant or lactating female or female / male who are planning to have children.
21. Insufficient adherence to participate in this clinical study.
22. Any other condition in which the investigator considers the patient unsuitable for this study.