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

Study summary

The goal of this YH42946-101 is to evaluate the safety, Tolerability, Pharmacokinetics and anti-tumor activity of YH42946 in patients with locally advanced of metastatic solid tumors with HER2 aberration and EGFR exon 20 insertions.

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedYH42946

The study team can explain what participation involves.

Who it may be forNon-small cell lung cancer (NSCLC) · EGFR · HER2

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Aug 17, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Recruiting

The study is currently accepting participants.

What kind of study?Phase 1 / Phase 2

Interventional

Where is it offered?8 U.S. locations

Locations may change over time.

Who runs it?Yuhan Corporation

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 1 / Phase 2
Sponsor: Yuhan Corporation
Interventions being studied: Drug: YH42946

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Locally advanced→Metastatic or stage IV→

Biomarkers

EGFR→HER2→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion 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 aberration 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.
Adequate Heart function: QTcF≤ 470 ms, LVEF≥ 50%
Blood Coagulation: INR or Prothrombin time ≤ 1.5 X ULN, aPTT ≤ 1.5 X ULN \[Dose Escalation part only\]
Histologically or cytologically confirmed diagnosis of advanced, and/or metastatic non-hematologic malignancy
Documented HER2 aberration or EGFR mutation (HER2 mutation or EGFR exon 20 insertion, HER2 amplification or overexpression) \[Dose Expansion part only\]
Patients who have at least 1 measurable lesion
Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC HER2 exon 20 insertion (Cohort 1)

Reasons someone may not be able to joinExclusion 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) infection, or active chronic hepatitis B or chronic hepatitis C
Major surgery within 4 weeks prior to the first dose of study treatment

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

Next Oncology VirginiaFairfax, Virginia
Seoul National University Bundang HospitalSeongnam-si, Gyeonggi-do
The Catholic Univ. of Korea St. Vincent's HospitalSuwon, Gyeonggi-do
Chungbuk National University HospitalCheongju-si, North Chungcheong
Seoul National University HospitalSeoul
Severance Hospital, Yonsei UniversitySeoul
Samsung Medical CenterSeoul
Asan Medical Center, University of UlsanSeoul

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Aug 17, 2026. Always confirm current availability with the study team.

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