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NSCLC (Non-small Cell Lung Cancer)Phase 1/2NCT06616766

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

A Phase 1/2 study testing YH42946 in people with NSCLC (Non-small Cell Lung Cancer) and Solid Tumor, run by Yuhan Corporation at 8 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
YH42946
Could I receive a placebo?
No, everyone receives an active treatment
How many people
201 participants
Where
8 sitesin 2 countries
Study dates
2 Oct 2024to 29 Jul 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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)

Who cannot join

  • 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
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  • 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) infection, or active chronic hepatitis B or chronic hepatitis C
  • Major surgery within 4 weeks prior to the first dose of study treatment

Trial locations and contacts

8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Yuhan Corporation Clinical Operation Team 1 contact

8228280576

clinicaltrials@yuhan.co.kr

8 sites in 2 countries

South Korea7 sites, 7 recruiting

  • Chungbuk National University Hospital

    Cheongju-si, North Chungcheong, 28644

    Ki-Hyeong Lee

    Ki-Hyeong Lee

    Recruiting

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

    Keun-wook Lee

    Recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Do-Youn Oh

    Recruiting

  • Severance Hospital, Yonsei University

    Seoul, 03722

    SunMin Lim

    Recruiting

  • Samsung Medical Center

    Seoul, 06351

    Sehoon Lee

    Recruiting

  • Asan Medical Center, University of Ulsan

    Seoul

    Dae Ho Lee

    Dae Ho Lee

    Recruiting

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

    Suwon, Gyeonggi-do, 16247

    Byoung Yong Shim

    Recruiting

Other trials in South Korea

United States1 site

  • Next Oncology Virginia

    Fairfax, Virginia, 22031

    Terminated

Other trials in United States

About this study

Official title: A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, PK and Anti-tumor Activity of YH42946 in Patients With Locally Advanced or Metastatic Solid Tumors With HER2 Aberration and EGFR Exon 20 Insertion

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.

Read the 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.

Being tested
YH42946
Keywords
YH42946-101
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • YH42946Drug

    YH42946

Study groups in NCT06616766
Study groupRoleWhat they receive
Part 1 and Part 2ExperimentalPart 1: Dose escalation arm to determine the MTD Part 2: Dose expansion part to select RD. Several independent cohorts are planned.
Receives: Drug: YH42946

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment Emergent Adverse Events(TEAE)s

    To assess the safety and tolerability of YH42946

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

  2. Objective Response Rate (ORR)

    Anti-tumor activity according to RECIST v1.1

    Measured: Through dose expansion part completion, approximately 12 months

Secondary outcomes (5)

  1. AUClast

    To characterize the pharmacokinetics (PK) of YH42946

    Measured: Through study completion, approximately 12 months

  2. AUCinf

    To characterize the pharmacokinetics (PK) of YH42946

    Measured: Through study completion, approximately 12 months

  3. Cmax

    To characterize the pharmacokinetics (PK) of YH42946

    Measured: Through study completion, approximately 12 months

  4. Tmax

    To characterize the pharmacokinetics (PK) of YH42946

    Measured: Through study completion, approximately 12 months

  5. Objective Response Rate (ORR)

    To assess the anti-tumor activity according to RECIST v1.1

    Measured: Through study completion, approximately 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2024
  2. Study start2 Oct 2024
  3. Primary completion15 Mar 2028 (estimated)
  4. Study completion29 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
201 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06616766
Sponsor's protocol ID
YH42946-101
Status last verified
Aug 2026
First submitted
23 Sep 2024
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. 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 A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing YH42946 in people with NSCLC (Non-small Cell Lung Cancer) and Solid Tumor, run by Yuhan Corporation at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yuhan Corporation Clinical Operation Team 1 (8228280576, clinicaltrials@yuhan.co.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Emergent Adverse Events(TEAE)s (time frame: Through study completion, during the first 21 days of DLT evaluation period.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06616766.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.

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