A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946

Inclusion Criteria: * ECOG performance status 0 or 1 * Estimated life expectancy of at least 3 months * Patients who have progressed on or after all available standard therapies or for whom standard treatment is inappropriate * Mandatory provision of archived or fresh tumor tissue in quantity sufficient to allow for retrospective confirmation of HER2 or EGFR mutation * A patient with a history of brain metastases must have had all lesions treated * Adequate organ function defined as all of the following: * Adequate bone marrow function (within 1 week prior to first administration): Neutrophils≥1.5 x10\*9 cells/L (Criteria must be met without the use of Granulocyte-Colony Stimulating Factor (G-CSF) within last week prior to testing.); platelet count≥75 x10\*9 cells/L; Hb ≥9g/dL (Criteria must be met without packed red blood cell (pRBC) transfusion within last week prior to testing.) * Adequate hepatic function: Serum bilirubin≤1.5 x upper limit of normal (ULN), and serum transaminase (either aspartate transaminase (AST) or alanine transaminase (ALT)) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases (within 1 week prior to first administration) * Adequate renal function: Serum creatinine ≤ 1.5 x ULN or Estimated glomerular filtration rate (eGFR) \> 60 mL/min per 1.73 m\*2 according to the site's calculation method. \[Dose Escalation part only\] * Histologically or cytologically confirmed diagnosis of advanced, and/or metastatic non-hematologic malignancy * Documented HER2 or EGFR mutation (HER2 mutation or EGFR exon 20 insertion, HER2 amplification or overexpression) \[Dose Expansion part only\] * Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC HER2 exon 20 insertion (Cohort 1) Exclusion Criteria: * Patient with symptomatic or progressive brain metastases * Known or suspected leptomeningeal disease (LMD) * Uncontrolled spinal cord compression * History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks * History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system * Medical, psychiatric, cognitive or other conditions that compromise the patients ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study * Any severe concurrent disease or condition (includes active infections, cardiac arrhythmia) that in the judgment of the Investigator would make study participation inappropriate for the patient * History of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required steroids, or any evidence of current ILD or pneumonitis * History of a second primary cancer with the exception of 1. curatively treated non-melanomatous skin cancer, 2. curatively treated cervical or breast carcinoma in situ, or 3. other malignancy with no known active disease present and no treatment administered during the last 2 years * Infection with human immunodeficiency virus (HIV) or prior hepatitis B or active chronic hepatitis B or active hepatitis C * Major surgery within 4 weeks prior to the first dose of study treatment