Clinical Trial of YH32367 in Patients With HER2 Positive Locally Advanced or Metastatic Solid Tumor
- Registration Number
- NCT05523947
- Lead Sponsor
- Yuhan Corporation
- 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-Ī³ 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 137
[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
- Cohort 1: Pathologically confirmed HER2-positive biliary tract cancer
- Cohort 2: Pathologically confirmed HER2-positive metastatic solid tumor malignancy other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description YH32367 YH32367 Dose Escalation Part: 8 Cohorts. In Dose Escalation part, patients are assigned to receive YH32367 at a starting dose and the dose being escalated/de-escalated in adjacent dose cohorts. Dose Expansion Part: 2 Cohorts (Cohort 1: Biliary tract cancer, Cohort 2: Solid tumors). Dose Expansion 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).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (11)
Southern Oncology Clinical Research Unit
š¦šŗAdelaide, Australia
Austin Health
š¦šŗMelbourne, Australia
Breast Cancer Research Centre - WA
š¦šŗPerth, Australia
Blacktown Hospital
š¦šŗSydney, Australia
CHA Bundang Medical Center
š°š·Seongnam, Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
š°š·Seoul, Korea, Republic of
Seoul National University Hospital
š°š·Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
š°š·Seoul, Korea, Republic of
Asan Medical Center
š°š·Seoul, Korea, Republic of
Samsung Medical Center
š°š·Seoul, Korea, Republic of
The Catholic University of Korea, St. Mary's hospital
š°š·Seoul, Korea, Republic of