Clinical trial NCT06975410: Clinical Trial of YH32364 in Patients With Locally Advanced or Metastatic EGFR Overexpressing Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: EGFR Overexpression
Locally Advanced Solid Tumor
Metastatic Solid Tumor
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
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

\* 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.

Exclusion Criteria:

* 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)
* 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

Primary outcomes:
measure: Treatment-emergent adverse events (TEAEs) including dose limiting toxicities (DLTs)
timeFrame: Study Day 1 to Study Day 28 (during the DLTs evaluation period)
measure: Objective Response Rate (ORR)
timeFrame: through dose expansion part completion, approximately 1.5 year
Secondary outcomes:
measure: Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: through study completion, approximately 2.5 year
measure: AUC from time 0 to infinity (AUCinf)
timeFrame: through study completion, approximately 2.5 year
measure: Maximum observed serum concentration (Cmax)
timeFrame: through study completion, approximately 2.5 year
measure: Time to reach Cmax (Tmax)
timeFrame: through study completion, approximately 2.5 year
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: through study completion, approximately 2.5 year
measure: Total clearance (CL)
timeFrame: through study completion, approximately 2.5 year
measure: Volume of distribution (Vd)
timeFrame: through study completion, approximately 2.5 year
measure: Volume of distribution at steady state (Vss)
timeFrame: through study completion, approximately 2.5 year
measure: AUC during dosing interval at steady state (AUCtau)
timeFrame: through study completion, approximately 2.5 year
measure: Cmax at steady state (Cmax,ss)
timeFrame: through study completion, approximately 2.5 year
measure: Time to reach Cmax,ss (Tmax,ss)
timeFrame: through study completion, approximately 2.5 year
measure: Accumulation ratio (Rac)
timeFrame: through study completion, approximately 2.5 year
measure: Trough (predose) serum concentration on Cycle 4 (Ctrough)
timeFrame: through study completion, approximately 2.5 year
measure: Presence and characterization of YH32364 ADA including neutralizing antibodies
timeFrame: through study completion, approximately 2.5 year
measure: Titer of YH32364 ADA
timeFrame: through study completion, approximately 2.5 year
measure: Objective Response Rate (ORR)
timeFrame: through dose escalation part completion, approximately 1 year
measure: Duration of Response (DoR)
timeFrame: through study completion, approximately 2.5 year
measure: Disease Control Rate (DCR)
timeFrame: through study completion, approximately 2.5 year
measure: Depth of Response
timeFrame: through study completion, approximately 2.5 year
measure: Time to Response
timeFrame: through study completion, approximately 2.5 year
measure: Progression-free survival (PFS)
timeFrame: through study completion, approximately 2.5 year
measure: TEAEs
timeFrame: through dose expansion part completion, approximately 1.5 year
measure: Overall Survival (OS)
timeFrame: through dose expansion part completion, approximately 1.5 year
Other outcomes:
measure: Immune ORR (iORR)
timeFrame: through study completion, approximately 2.5 year
measure: Immune Duration of Response (iDOR)
timeFrame: through study completion, approximately 2.5 year
measure: Immune PFS (iPFS)
timeFrame: through study completion, approximately 2.5 year
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Yuhan Corporation
name: Yuhan Clinical Research Physician
role: STUDY_DIRECTOR
References: