Neratinib and Trastuzumab Biosimilar in Patients with HER2 Mutated Advanced Solid Cancers

Inclusion Criteria:

* Patients who voluntarily decide to participate and give written consent after hearing the explanation of the clinical trial and investigational drugs.
* Adult men and women over 19 years old.
* Histological or cytological confirmed advanced solid tumor and confirmed to have HER2 known oncogenic mutations in tumor DNA by K-master panel test using tumor tissues or circulating tumor DNA in blood.
* Patients having at least 1 or more than 1 measurable lesion according to RECIST v 1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status 0\~2.
* Patients whose life expectancy is more than 6 months.
* Metastatic/progressive solid cancer patients who have received one or more than one standard treatment or do not have any treatment option.
* Patients who have agreed to provide plasma/blood samples, the most recent metastatic/progressive tumor sample or new tumor biopsy for gene sequencing and other biomarker analysis.

Exclusion Criteria:

* Patients who received radiotherapy or surgical treatment within 2 weeks prior to the initiation of investigational product.
* Patients having symptomatic brain metastasis who needs treatment. Patients with stable brain metastasis who need no treatment including steroid are eligible
* Inappropriate HER2 mutation (e.g., non-Hot Spot mutation, variant of unknown siginificance, subclonal mutation, premature STOP codon or the Frame Shift mutation).
* Patients having difficulties in swallowing tablets.
* Patients with toxicities of prior treatment which are not recovered to baseline level or ≤ Grade 1.
* Inadequate organ functions:

  1. Hemoglobin (Hemoglobin) \< 8 .0g / dL
  2. Absolute neutrophil count (ANC) \< 1. 0 x10 ³ per mm³
  3. Platelet count \< 100 x10⁹/L (100 ,000/ mm³)
  4. Total bilirubin \> 1.5 x upper normal limits (UNL), (exclude Gilbert's syndrome)
  5. Alanine aminotransferase (ALT) or aspartate amino transferase (AST) \> 3 x upper normal limits (UNL) (in case of liver and bone metastases \> 5 x ULN)
  6. Serum creatinine \>1.5 x upper normal limits (UNL) or \< eGFR 30 mL/min/1.73 m² 7) Left ventricle ejection fraction \<50% by multi-gate obtaining method scan (MUGA) or echocardiogram.

  8\) Chronic gastrointestinal disorders of which a main symptom is diarrhea (e.g., Crohn's disease, malabsorption, or grade 2 or more than grade 2 diarrhea according to the NCI CTCAE version 5.0 regardless of etiology).