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

NCT ID: NCT06616766

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-02
• Study Completion Date: 2028-07-29

Brief 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.

Detailed Description

YH42946 is a novel, orally available tyrosine kinase inhibitor targeting HER2. YH42946 showed potency for diverse HER2 aberrations including HER2 overexpression, amplification, or mutation, as well as EGFR Ex20ins.

This is a Phase 1/2, open-label, multicenter, first-in-human study of YH42946. The study has 2 parts. The first part is dose escalation part to identify the maximum tolerated dose. The second part is dose expansion part to select 2 doses for RD selection at the first cohort, after then RD will be determined to ensure its efficacy. Several independent cohorts are planned.

Conditions

NSCLC (Non-small Cell Lung Cancer); Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 and Part 2

Part 1: Dose escalation arm to determine the MTD Part 2: Dose expansion part to select RD. Several independent cohorts are planned.

Group Type: EXPERIMENTAL

YH42946

Intervention Type: DRUG

YH42946

Interventions

YH42946

YH42946

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yuhan Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Ertle, MD

Role: STUDY_DIRECTOR

Yuhan Corporation

Locations

Next Oncology Virginia

Fairfax, Virginia, United States

Site Status: RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status: RECRUITING

The Catholic Univ. of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Site Status: RECRUITING

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, South Korea

Site Status: RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status: RECRUITING

Severance Hospital, Yonsei University

Seoul, , South Korea

Site Status: RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status: RECRUITING

Asan Medical Center, University of Ulsan

Seoul, , South Korea

Site Status: RECRUITING

Countries

United States; South Korea

Central Contacts

Yuhan Corporation Clinical Operation Team 1

Role: CONTACT

clinicaltrials@yuhan.co.kr

8228280576

Facility Contacts

Alexander I. Spira

Role: primary

Keun-wook Lee

Role: primary

Byoung Yong Shim

Role: primary

Ki-Hyeong Lee

Role: primary

Do-Youn Oh

Role: primary

Byoung Chul Cho

Role: primary

Sehoon Lee

Role: primary

Sang-We Kim

Role: primary

Other Identifiers

YH42946-101

Identifier Type: -

Identifier Source: org_study_id