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 forwhom standard treatment is inappropriate

• Mandatory provision of archived or fresh tumor tissue in quantity sufficient toallow 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 x109 cells/L (Criteria must be met without the use ofGranulocyte-Colony Stimulating Factor (G-CSF) within last week prior totesting.); platelet count≥75 x109 cells/L; Hb ≥9g/dL (Criteria must be metwithout packed red blood cell (pRBC) transfusion within last week prior totesting.)

• Adequate hepatic function: Serum bilirubin≤1.5 x upper limit of normal (ULN),and serum transaminase (either aspartate transaminase (AST) or alaninetransaminase (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 glomerularfiltration rate (eGFR) > 60 mL/min per 1.73 m*2 according to the site'scalculation method.

[Dose Escalation part only]

• Histologically or cytologically confirmed diagnosis of advanced, and/or metastaticnon-hematologic malignancy

• Documented HER2 or EGFR mutation (HER2 mutation or EGFR exon 20 insertion, HER2amplification or overexpression)

[Dose Expansion part only]

• Patients with histologically or cytologically confirmed locally advanced ormetastatic 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, coronaryartery 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 YorkHeart Association (NYHA) functional classification system

• Medical, psychiatric, cognitive or other conditions that compromise the patientsability to understand the patient information, to give informed consent, to complywith the study protocol or to complete the study

• Any severe concurrent disease or condition (includes active infections, cardiacarrhythmia) that in the judgment of the Investigator would make study participationinappropriate for the patient

• History of (non-infectious) interstitial lung disease (ILD) or pneumonitis thatrequired 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 treatmentadministered during the last 2 years

• Infection with human immunodeficiency virus (HIV) or prior hepatitis B or activechronic hepatitis B or active hepatitis C

• Major surgery within 4 weeks prior to the first dose of study treatment