A Study of RC48-ADC Combined With Pyrotinib For Treatment of Local Advanced or Metastasis NSCLC With HER2 Mutation

An Open-label, Single-center, Phase Ib/II Study to Evaluate the Safety, Efficacy and Pharmacokinetics of RC48-ADC Combined With Pyrotinib in Local Advanced or Metastasis NSCLC With HER2 Mutation

This study will evaluate the efficacy, safety and pharmacokinetics of RC48-ADC for injection combined with pyrotinib in subjects with local advanced or metastatic non-small cell lung cancer with HER2 mutation.

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Predicted survival ≥ 12 weeks.
• According to UICC/AJCC 8th Edition, histologically and/or cytologically-confirmed, cannot be surgically removed, locally advanced or metastatic NSCLC.
• Is willing and able to provide an adequate archival tumor tissue sample
• Has relapsed from or is refractory to standard treatment and had received both platinum-based therapy and immunotherapy.
• Measurable lesion according to RECIST 1.1.
• Documented HER2 exon 20 insertion mutation.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function.
• 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:

• No known EGFR, ALK, ROS1, RET, NTRK, MET 14 or BRAF V600E mutation.
• Patient has had previous treatment with HER2-targeted therapy prior to study participation.
• History of major surgery within 4 weeks of planned start of trial treatment.
• Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive, or HIVAb positive.
• Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
• NYHA Class III heart failure.
• Suffering from active infection requiring systemic treatment.
• Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD.
• Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment.