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

NCT06616766 | Recruiting Phase 1 FDA Drug

• 1 other identifier: YH42946-101
• Study Type: interventional
• Target: 161
• Locations: 2 countries
• Sites: 8

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.

Conditions

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

Keywords

YH42946-101

Outcome Measures

Primary Outcomes (2)

• Treatment Emergent Adverse Events(TEAE)s

  To assess the safety and tolerability of YH42946

  Through study completion, during the first 21 days of DLT evaluation period.

• Objective Response Rate (ORR)

  Anti-tumor activity according to RECIST v1.1

  Through dose expansion part completion, approximately 12 months

Secondary Outcomes (5)

• AUClast

  Through study completion, approximately 12 months

• AUCinf

  Through study completion, approximately 12 months

• Cmax

  Through study completion, approximately 12 months

• Tmax

  Through study completion, approximately 12 months

• Objective Response Rate (ORR)

  Through study completion, approximately 12 months

Other Outcomes (1)

• Overall survival(OS)

  Through study completion, approximately 3.5 year

Study Arms (1)

Part 1 and Part 2

EXPERIMENTAL

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

Drug: YH42946

Interventions

YH42946 DRUG

YH42946

Part 1 and Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• curatively treated non-melanomatous skin cancer,
• curatively treated cervical or breast carcinoma in situ, or
• 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

Sponsors & Collaborators

• Yuhan Corporation: lead

Study Sites (8)

Next Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

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

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Asan Medical Center, University of Ulsan

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Judith Ertle, MD

  Yuhan Corporation

  STUDY DIRECTOR

Central Study Contacts

Yuhan Corporation Clinical Operation Team 1

CONTACT

8228280576; clinicaltrials@yuhan.co.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: September 27, 2024
• Study Start: October 2, 2024
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): July 29, 2028
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 1 year and ending 5 years after all trial endpoints were assessed
• Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to clinicaltrials@yuhan.co.kr

Locations

US (1); KR (7)