RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05523947Sponsor: Yuhan CorporationLast updated: 2026-06-11

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.

Arms & 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.

Outcome measures

Primary

Treatment-emergent adverse events (TEAEs) up to Day 21
To assess the safety and tolerability of YH32367
Time frame: 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)
Time frame: through dose expansion part completion, approximately 2.5 year

Secondary

Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
Time frame: up to 66 weeks
maximum observed serum concentration (Cmax)
Time frame: up to 66 weeks
time to reach Cmax (Tmax)
Time frame: up to 66 weeks
Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies
Time frame: through study completion, approximately 3.5 year
Objective Response Rate (ORR)
Time frame: through study completion, approximately 3.5 year
Duration of Response (DoR)
Time frame: through study completion, approximately 3.5 year
Disease Control Rate (DCR)
Time frame: through study completion, approximately 3.5 year
Depth of Response
Time frame: through study completion, approximately 3.5 year
Time to Response
Time frame: through study completion, approximately 3.5 year
Progression-free survival (PFS)
Time frame: through study completion, approximately 3.5 year
TEAEs
Time frame: through dose expansion part completion, approximately 2.5 year
Overall Survival (OS)
Time frame: through study completion, approximately 3.5 year

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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

Study locations (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232

Recruiting