EGFR Overexpression, Locally Advanced Solid Tumor, Metastatic Solid Tumor
Conditions
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
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.
Interventions
DRUGYH32364
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)
Sponsors
Yuhan Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) including dose limiting toxicities (DLTs) | Study Day 1 to Study Day 28 (during the DLTs evaluation period) | To assess the safety and tolerability of YH32364 in order to determine maximum tolerated dose (MTD) and select doses for dose optimization |
| Objective Response Rate (ORR) | through dose expansion part completion, approximately 1.5 year | To assess the ORR of YH32364 at the recommended dose (RD) according to RECIST v1.1 by Investigator assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| AUC from time 0 to infinity (AUCinf) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Maximum observed serum concentration (Cmax) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Time to reach Cmax (Tmax) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Apparent terminal elimination half-life (t1/2) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Total clearance (CL) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Volume of distribution (Vd) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Volume of distribution at steady state (Vss) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| AUC during dosing interval at steady state (AUCtau) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Cmax at steady state (Cmax,ss) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Time to reach Cmax,ss (Tmax,ss) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Accumulation ratio (Rac) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Trough (predose) serum concentration on Cycle 4 (Ctrough) | through study completion, approximately 2.5 year | To characterize the pharmacokinetics (PK) of YH32364 |
| Presence and characterization of YH32364 ADA including neutralizing antibodies | through study completion, approximately 2.5 year | To explore the immunogenicity of YH32364 |
| Titer of YH32364 ADA | through study completion, approximately 2.5 year | To explore the immunogenicity of YH32364 |
| Objective Response Rate (ORR) | through dose escalation part completion, approximately 1 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| Duration of Response (DoR) | through study completion, approximately 2.5 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| Disease Control Rate (DCR) | through study completion, approximately 2.5 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| Depth of Response | through study completion, approximately 2.5 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| Time to Response | through study completion, approximately 2.5 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| Progression-free survival (PFS) | through study completion, approximately 2.5 year | To assess the anti-tumor activity according to RECIST v1.1 by Investigator assessment |
| TEAEs | through dose expansion part completion, approximately 1.5 year | To assess the safety and tolerability of YH32364 |
| Overall Survival (OS) | through dose expansion part completion, approximately 1.5 year | To assess the overall survival of YH32364 at the RD |
Countries
South Korea
Contacts
CONTACTClinical Operation Team 1
CONTACTChaebin Lee
STUDY_DIRECTORYuhan Clinical Research Physician
Yuhan Corporation
Outcome results
None listed