Clinical Trial of YH32367 in Patients With HER2 Positive Locally Advanced or Metastatic Solid Tumor

A Phase 1/2, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of YH32367 in Patients With HER2-Positive Locally Advanced or Metastatic Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-Positive Solid Tumor
• Intervention / Treatment: Drug: YH32367

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.

• Study Type: Interventional
• Enrollment (Estimated): 147
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operation Team 1; Phone Number: +82-2-828-0858; Email: clinicaltrials@yuhan.co.kr
• Study Contact Backup: Name: Jiyong Park; Phone Number: +82-2-828-0858; Email: pjy0422@yuhan.co.kr

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Southern Oncology Clinical Research Unit
  • Melbourne, Australia
    • Recruiting
    • Austin Health
  • Perth, Australia
    • Withdrawn
    • Breast Cancer Research Centre - WA
  • Sydney, Australia
    • Recruiting
    • Blacktown Hospital
• South Korea
  • Incheon, South Korea, 21565
    • Recruiting
    • Gachon Gil University Medical Center
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 02841
    • Recruiting
    • Korea University Anam Hospital
  • Seoul, South Korea, 06591
    • Recruiting
    • The Catholic University of Korea, St. Mary's Hospital
  • Ulsan, South Korea, 44437
    • Recruiting
    • Ulsan University Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13496
      • Recruiting
      • CHA Bundang Medical Center
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Recruiting
      • Ajou University Hospital
    • Suwon, Gyeonggi-do, South Korea, 16247
      • Recruiting
      • Catholic University of Korea St. Vincent's Hospital
  • Gyeongsangnam-do
    • Jinju, Gyeongsangnam-do, South Korea, 52727
      • Recruiting
      • Gyeongsang National University Hospital
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea, 28644
      • Recruiting
      • Chungbuk National University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Drug: YH32367; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events (TEAEs) up to Day 21	To assess the safety and tolerability of YH32367	in dose escalation part, an average of 21 days
Objective Response Rate (ORR)	To assess the ORR of YH32367 at the recommended Phase 2 dose (RP2D) according to RECIST v1.1 by blinded independent central reviews (BICR)	through dose expansion part completion, approximately 2.5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)	To characterize the PK of YH32367	up to 66 weeks
maximum observed serum concentration (Cmax)	To characterize the PK of YH32367	up to 66 weeks
time to reach Cmax (Tmax)	To characterize the PK of YH32367	up to 66 weeks
Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies	To explore the immunogenicity of YH32367	through study completion, approximately 3.5 year
Objective Response Rate (ORR)	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Duration of Response (DoR)	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Disease Control Rate (DCR)	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Depth of Response	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Time to Response	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Progression-free survival (PFS)	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
TEAEs	To assess the safety and tolerability of YH32367 at the RP2D	through dose expansion part completion, approximately 2.5 year
Overall Survival (OS)	To assess overall survival of YH32367	through study completion, approximately 3.5 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune ORR (iORR)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year
Immune Duration of Response (iDOR)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year
Immune PFS (iPFS)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Principal Investigator: Do-Youn Oh, Seoul National University Hospital; Principal Investigator: Ganessan Kichenadasse, Southern Oncology Clinical Research Unit; Principal Investigator: Jennifer Man, Blacktown Hospital; Principal Investigator: Arlene Chan, Breast Cancer Research Centre WA; Principal Investigator: Ju Won Kim, Korea University Anam Hospital; Principal Investigator: Myung Ah Lee, The Catholic University of Korea, St. Mary's Hospital; Principal Investigator: Hongjae Chon, CHA Bundang Medical Center; Principal Investigator: Niall Tebbutt, Austin Health; Principal Investigator: Joon Oh Park, Samsung Medical Center; Principal Investigator: Jung Hun Kang, Gyeongsang National University Hospital; Principal Investigator: Seok Yun Kang, Ajou University School of Medicine; Principal Investigator: Hyung Soon Park, Catholic University of Korea St. Vincent's Hospital; Principal Investigator: Ji Hong Bae, Gachon Gil University Medical Center; Principal Investigator: Cheol Kyung Sin, Ulsan University Hospital; Principal Investigator: Hae Seong Park, Dana-Farber Cancer Institute; Principal Investigator: Thatcher Heumman, Vanderbilt-Ingram Cancer Center; Principal Investigator: Kyu-pyo Kim, Asan Medical Center; Principal Investigator: Hongsik Kim, Chungbuk National University Hospital; Principal Investigator: Hyejin Choi, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Gastric cancer; Breast cancer; Solid tumor; HER2-positive; Biliary tract cancer; YH32367; HER2/4-1BB bispecific antibody
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Biliary Tract Diseases; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Stomach Neoplasms; Biliary Tract Neoplasms; Breast Neoplasms
• Other Study ID Numbers: YH32367-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to andrew90@yuhan.co.kr.

A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

• IPD Sharing Time Frame: Beginning 1 year and ending 5 years after all trial endpoints were assessed
• IPD Sharing Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to andrew90@yuhan.co.kr.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No