HER2-Positive Solid Tumor
Conditions
Keywords
YH32367, HER2/4-1BB bispecific antibody, Solid tumor, Breast cancer, Gastric cancer, HER2-positive, Biliary tract cancer
Brief summary
This first-in-human study will be counducted to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of YH32367 in Patients with HER2-Positive Locally Advanced or Metastatic Solid Tumors.
Detailed description
YH32367, a novel HER2/4-1BB bispecific antibody (BsAb), simultaneously targets HER2 and h4-1BB and binds to both targets. YH32367 exhibits a strong 4-1BB signal activation as well as blocking of HER2 signaling in HER2-expressing tumor cells. YH32367 stimulates IFN-γ secretion from T cells and thereby induces tumor cells lysis. This is a Phase 1/2, open-label, multicenter, first-in-human study of YH32367. This 2-part study will include both a Dose Escalation part, to identify the Maximum Tolerated Dose (MTD) and/or two dose levels for RP2D selection, and a Dose Expansion part, to determine RP2D and to confirm the safety, tolerability and efficacy of YH32367 at the RP2D.
Interventions
DRUGYH32367
Dose Escalation Part: 8 Cohorts. In this part, approximately 30 patients will be enrolled and patients are assigned to receive YH32367 at a starting dose and the dose being escalated/de-escalated in adjacent dose cohorts will be up to Dose level 8. Dose Expansion Part: 2 Cohorts(Cohort 1: Biliary tract cancer, Cohort 2: Solid tumors). The part will consist of multiple cohorts in patients who were treated with at least 1 prior gemcitabine- and/or cisplatin-based therapy, HER2 positive biliary tract cancer(Cohort 1); in patients who were treated with all available standard therapies and have no available options, HER2 positive solid tumor malignancies other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer(Cohort 2). Each cohort will enroll approximately 75 and 40 patients, respectively.
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
\[Dose Escalation Part\] * Pathologically confirmed HER2-positive * Mandatory provision of tumor tissue sample \[Dose Expansion Part\] * Patients who have at least one measurable lesion * Mandatory provision of tumor tissue sample 1. Cohort 1: Pathologically confirmed HER2-positive biliary tract cancer 2. Cohort 2: Pathologically confirmed HER2-positive metastatic solid tumor malignancy other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer
Exclusion criteria
* Uncontrolled central nervous system (CNS) metastases * Spinal cord compression * Carcinomatous meningitis * Acute coronary syndromes * Heart failure * Interstitial lung disease (ILD) * Pneumonitis * History of a second primary cancer * Human immunodeficiency virus (HIV) * Active chronic hepatitis B * Hepatitis C * Systemic steroid therapy * Autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) up to Day 21 | in dose escalation part, an average of 21 days | To assess the safety and tolerability of YH32367 |
| Objective Response Rate (ORR) | through dose expansion part completion, approximately 2.5 year | To assess the ORR of YH32367 at the recommended Phase 2 dose (RP2D) according to RECIST v1.1 by blinded independent central reviews (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast) | up to 66 weeks | To characterize the PK of YH32367 |
| maximum observed serum concentration (Cmax) | up to 66 weeks | To characterize the PK of YH32367 |
| time to reach Cmax (Tmax) | up to 66 weeks | To characterize the PK of YH32367 |
| Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies | through study completion, approximately 3.5 year | To explore the immunogenicity of YH32367 |
| Objective Response Rate (ORR) | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| Duration of Response (DoR) | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| Disease Control Rate (DCR) | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| Depth of Response | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| Time to Response | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| Progression-free survival (PFS) | through study completion, approximately 3.5 year | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment |
| TEAEs | through dose expansion part completion, approximately 2.5 year | To assess the safety and tolerability of YH32367 at the RP2D |
| Overall Survival (OS) | through study completion, approximately 3.5 year | To assess overall survival of YH32367 |
Countries
Australia, South Korea, United States
Contacts
CONTACTClinical Operation Team 1
CONTACTHeayeon Yoo
PRINCIPAL_INVESTIGATORHyejin Choi
Severance Hospital
PRINCIPAL_INVESTIGATORKyu-pyo Kim
Asan Medical Center
PRINCIPAL_INVESTIGATORDo-Youn Oh
Seoul National University Hospital
PRINCIPAL_INVESTIGATORJoon Oh Park
Samsung Medical Center
PRINCIPAL_INVESTIGATORGanessan Kichenadasse
Southern Oncology Clinical Research Unit
PRINCIPAL_INVESTIGATORJennifer Man
Blacktown Hospital
PRINCIPAL_INVESTIGATORArlene Chan
Breast Cancer Research Centre WA
PRINCIPAL_INVESTIGATORJu Won Kim
Korea University Anam Hospital
PRINCIPAL_INVESTIGATORMyung Ah Lee
The Catholic University of Korea, St. Mary's hospital
PRINCIPAL_INVESTIGATORHongjae Chon
CHA Bundang Medical Center
PRINCIPAL_INVESTIGATORNiall Tebbutt
Austin Health
PRINCIPAL_INVESTIGATORJung Hun Kang
Gyeongsang National University Hospital
PRINCIPAL_INVESTIGATORSeok Yun Kang
Ajou University School of Medicine
PRINCIPAL_INVESTIGATORHyung Soon Park
Catholic University of Korea St. Vincent's Hospital
PRINCIPAL_INVESTIGATORJi Hong Bae
Gachon Gil University Medical Center
PRINCIPAL_INVESTIGATORCheol Kyung Sin
Ulsan University Hospital
PRINCIPAL_INVESTIGATORHae Seong Park
Dana-Farber Cancer Institute
PRINCIPAL_INVESTIGATORThatcher Heumman
Vanderbilt-Ingram Cancer Center
PRINCIPAL_INVESTIGATORHongsik Kim
Chungbuk National University Hospital
Outcome results
None listed