YH32364 for locally advanced or metastatic EGFR‑overexpressing solid tumors
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 trial will test whether YH32364 can help adults with advanced or metastatic cancers that overexpress EGFR when other treatments haven't worked.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Yuhan Corporation Industry-sponsored |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 4 sites (Seoul and 3 other locations) |
| Trial ID | NCT06975410 on ClinicalTrials.gov |
What this trial studies
YH32364 is a bispecific antibody designed to both block EGFR signaling and activate the immune co‑stimulatory receptor 4‑1BB specifically in tumors to boost T cell responses while aiming to reduce liver toxicity seen with earlier 4‑1BB agonists. The study has a Phase 1 dose‑escalation part with up to six dose levels to identify safe doses, followed by a randomized Phase 2 part comparing two selected dose levels to confirm the recommended dose. Treatment is given by IV infusion every two weeks with regular on‑site assessments for safety and tumor measurements. Eligible adults have locally advanced or metastatic solid tumors confirmed to overexpress EGFR and have exhausted standard therapy options.
Who should consider this trial
Good fit: Adults (≥18 years) with locally advanced or metastatic solid tumors confirmed to overexpress EGFR (IHC 2+ or 3+), ECOG 0–1, measurable disease, life expectancy ≥3 months, and disease refractory or intolerant to available standard therapies are ideal candidates.
Not a fit: Patients without EGFR overexpression, with ECOG >1, who have effective standard treatment options still available, or who cannot attend frequent IV infusions and assessments are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, YH32364 could shrink or slow growth of EGFR‑overexpressing tumors by blocking EGFR and enhancing anti‑tumor T cell activity while potentially avoiding prior liver side effects of 4‑1BB drugs.
How similar studies have performed: EGFR‑targeted drugs and 4‑1BB agonists have shown activity previously, but the EGFR/4‑1BB bispecific approach is novel with promising preclinical data and limited clinical proof to date.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Seoul and 3 other locations
- Korea University Anam Hospital — Seoul, South Korea (Recruiting)
- Seoul National University Hospital — Seoul, South Korea (Recruiting)
- Severance Hospital — Seoul, South Korea (Recruiting)
- Samsung Medical Center — Seoul, South Korea (Recruiting)
Study contacts
- Study coordinator: Clinical Operation Team 1
- Email: clinicaltrials@yuhan.co.kr
- Phone: +82-2-828-0712
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.