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

Recruitment & Eligibility

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.
1. 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).

Study & Design

Arm && Interventions

Group	Intervention	Description
A arm	Neratinib Maleate	Neratinib + herzuma

Primary Outcome Measures

Name	Time	Method
overall response rate (ORR)	at 6 months	ORR according to RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
clinical benefit rate, CBR	at 6 months	CR+PR + SD more than 12 weeks
median duration of response, DOR	at 6 months	DOR is related to the quality of life and is one of the methods for evaluating tumor response approved by pharmaceutical regulatory agencies
median progression free survival, PFS	at 6 months	from enrollment to disease progression, death or withdrawal
safety profiles	at 6 months	safety profiles according to CTCAE 4.0

Recruitment & Eligibility