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

Yuhan

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: HER2-Positive Solid Tumor

Treatments: Drug: YH32367

Study type: Interventional

Funder types: Industry

Identifiers

NCT05523947

YH32367-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 137 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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137 participants in 1 patient group

YH32367

Experimental group

Description:

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).

Treatment:

Drug: YH32367