EGFR OverexpressionPhase 1/2NCT06975410
Clinical Trial of YH32364 in Patients With Locally Advanced or Metastatic EGFR Overexpressing Solid Tumors
A Phase 1/2 study testing YH32364 in people with EGFR Overexpression and Locally Advanced Solid Tumor, run by Yuhan Corporation at 4 sites in South Korea.
Trial summary
This is a study for people with locally advanced or metastatic cancer for whom previous treatment was not successful. Adults aged 18 and over with advanced cancer with Epidermal Growth Factor Receptor (EGFR) overexpressing can join the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR Overexpression, Locally Advanced Solid Tumor, Metastatic Solid Tumor
- What is being tested?
- YH32364
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 4 sitesSouth Korea
- Study dates
- 12 Jun 2025to Dec 2029
- Phase
- Phase 1/2
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
- Must sign an informed consent form (ICF) prior to any study specific procedures
- ECOG performance status 0 or 1
- Estimated life expectancy of at least 3 months
- A woman must not be breastfeeding
- Have at least one measurable lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline ≥10 mm in the longest diameter (except lymph nodes which must have a short axis of ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), are suitable for accurate repeated measurements.
- [Dose Escalation Only] Locally advanced or metastatic EGFR overexpressing solid tumor that is refractory or intolerable on all available standard therapy and that is considered uncurable by local therapy
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- One of the following pathologically confirmed EGFR overexpressing (IHC3+ or IHC2+) tumors.
- Head and neck squamous cell carcinoma (HNSCC)
- Non-small cell lung cancer (NSCLC): squamous cell carcinoma (SqCC)
- Esophageal squamous cell carcinoma (ESCC)
- Biliary tract cancer (BTC)
- Uterine cervical cancer
- Vulvar cancer
- Urothelial cancer
- Squamous cell carcinoma of other origin of tumor (e.g., skin squamous cell tumor)
- [Dose Expansion Only] Cohort 1: Pathologically confirmed EGFR overexpressing (IHC3+ or IHC2+), locally advanced or metastatic HNSCC other than nasopharyngeal carcinoma (NPC) that is refractory or intolerable on all available standard therapy and that is considered uncurable by local therapy.
Who cannot join
- Known uncontrolled central nervous system (CNS) metastases, spinal cord compression, and/or carcinomatous meningitis
- Have 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
- Have history of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA)
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- Have history of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks
- Have history of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required steroids, or any evidence of current ILD or pneumonitis
- Have autoimmune disease that has required systemic treatment
- Infection with human immunodeficiency virus (HIV)
- Active chronic hepatitis B or chronic hepatitis C
- [Prior/Concomitant Therapy]
- Have received systemic steroid therapy
- Previous treatment with a 4-1BB/CD137-modulating agent
- Have used a live vaccine within 4 weeks
- Have received treatment with immunotherapy, biological therapies, targeted small molecules, or hormonal therapies
- Have received radiation therapy
- Have received cytotoxic chemotherapy
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea4 sites, 4 recruiting
- Recruiting
Korea University Anam Hospital
Seoul, 02841
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital
Seoul, 03722
- Recruiting
Samsung Medical Center
Seoul, 06351
About this study
Official title: A Phase 1/2, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of YH32364 in Patients With Locally Advanced or Metastatic Solid Tumors
This is a study for people with locally advanced or metastatic cancer for whom previous treatment was not successful. Adults aged 18 and over with advanced cancer with Epidermal Growth Factor Receptor (EGFR) overexpressing can join the study. The purpose of this study is to find out whether a medicine called YH32364 helps people with locally advanced or metastatic cancers with EGFR overexpression.
Read the detailed description
YH32364 is a new type of immunotherapy called a bispecific antibody that targets both Epidermal Growth Factor Receptor (EGFR) and 4-1BB. EGFR is a gene involved in cancer growth, and many cancer treatments aim to target it. 4-1BB, an immune-modulating protein, plays an important role in boosting T cell activity to combat cancer.
YH32364 is a treatment designed to activate 4-1BB specifically in tumors, aiming to avoid the liver-related side effects seen with previous 4-1BB treatments. It also helps block EGFR signals, assumed to make EGFR-targeted therapies more effective by overcoming resistance.
This study is consists of two parts. In Part 1, participants will be assigned sequentially to one of six dose levels, ranging from the lowest to the highest dose as determined by the sponsor, in order to identify an appropriate dosage.
In Part 2, participants will be randomly assigned to one of the two optimal dose levels identified in Part 1 to confirm the recommended dose.
The YH32364 will be administered via intravenous (IV) infusion once every two weeks. Participants will be required to visit the study site regularly for treatment and assessments. During all the visits, the doctors check participants' health and take note of any unwanted effects.
- Being tested
- YH32364
- Keywords
- YH32364, EGFR/4-1BB bispecific antibody, Solid tumor, Head and neck squamous cell carcinoma (HNSCC), Non-small cell lung cancer (NSCLC), Esophageal squamous cell carcinoma (ESCC), Biliary tract cancer (BTC), Uterine cervical cancer, Vulvar cancer, Urothelial cancer
- Medical subject headings
- Neoplasm Metastasis, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Esophageal Squamous Cell Carcinoma, Biliary Tract Neoplasms, Uterine Cervical Neoplasms, Vulvar Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YH32364Drug
Dose Escalation Part: In this part, 6 dose levels are planned and approximately 30 patients will be enrolled. After each dose level, Safety Review Committee (SRC) will evaluate the available safety, tolerability, PK of YH32364 to decide the next dose.
Dose Expansion Part: 50 participants with previously treated locally advanced or metastatic EGFR overexpressing HNSCC other than NPC will be randomized 1:1 ratio to each dose. (Cohort 1: Participants with locally advanced or metastatic EGFR overexpressing HNSCC other than NPC, whose disease progressed after or who are intolerable to all the available standard treatment)
| Study group | Role | What they receive |
|---|---|---|
| YH32364 | Experimental | Dose Escalation Part: Dose Escalation part is designed to assess the safety and tolerability of YH32364 and to identify the Maximum Tolerated dose (MTD) and/or two dose levels for recommended dose (RD) selection.
Dose Expansion Part: Dose Expansion part will consist of multiple cohorts by cancer types. Cohort 1 will be initiated to determine the RD after completion of Part 1. The RD will be determined among two dose levels investigated in Cohort 1 based on the totality of available data including PK, biomarkers, dose-response, safety, and efficacy. Receives: Drug: YH32364 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent adverse events (TEAEs) including dose limiting toxicities (DLTs)
To assess the safety and tolerability of YH32364 in order to determine maximum tolerated dose (MTD) and select doses for dose optimization
Measured: Study Day 1 to Study Day 28 (during the DLTs evaluation period)
Objective Response Rate (ORR)
To assess the ORR of YH32364 at the recommended dose (RD) according to RECIST v1.1 by Investigator assessment
Measured: through dose expansion part completion, approximately 1.5 year
Secondary outcomes (23)
Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
AUC from time 0 to infinity (AUCinf)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Maximum observed serum concentration (Cmax)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Time to reach Cmax (Tmax)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Apparent terminal elimination half-life (t1/2)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Total clearance (CL)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Volume of distribution (Vd)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Volume of distribution at steady state (Vss)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
AUC during dosing interval at steady state (AUCtau)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Cmax at steady state (Cmax,ss)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Time to reach Cmax,ss (Tmax,ss)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Accumulation ratio (Rac)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Trough (predose) serum concentration on Cycle 4 (Ctrough)
To characterize the pharmacokinetics (PK) of YH32364
Measured: through study completion, approximately 2.5 year
Presence and characterization of YH32364 ADA including neutralizing antibodies
To explore the immunogenicity of YH32364
Measured: through study completion, approximately 2.5 year
Titer of YH32364 ADA
To explore the immunogenicity of YH32364
Measured: through study completion, approximately 2.5 year
Objective Response Rate (ORR)
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through dose escalation part completion, approximately 1 year
Duration of Response (DoR)
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through study completion, approximately 2.5 year
Disease Control Rate (DCR)
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through study completion, approximately 2.5 year
Depth of Response
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through study completion, approximately 2.5 year
Time to Response
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through study completion, approximately 2.5 year
Progression-free survival (PFS)
To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment
Measured: through study completion, approximately 2.5 year
TEAEs
To assess the safety and tolerability of YH32364
Measured: through dose expansion part completion, approximately 1.5 year
Overall Survival (OS)
To assess the overall survival of YH32364 at the RD
Measured: through dose expansion part completion, approximately 1.5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2025
- Study start12 Jun 2025
- Primary completionJun 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFR OverexpressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yuhan Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yuhan Clinical Research Physician, Study director, Yuhan Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06975410
- Sponsor's protocol ID
- YH32364-101
- Status last verified
- Jun 2026
- First submitted
- 28 Apr 2025
- Last updated
- 10 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- 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.