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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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 tr

Первичные конечные точки

• Treatment-emergent adverse events (TEAEs) up to Day 21 [Срок оценки: in dose escalation part, an average of 21 days]
• Objective Response Rate (ORR) [Срок оценки: through dose expansion part completion, approximately 2.5 year]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

\[Dose Escalation Part\]

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 13 центров

• CHA Bundang Medical Center — Seongnam-si
• Catholic University of Korea St. Vincent's Hospital — Suwon
• Ajou University Hospital — Suwon
• Gyeongsang National University Hospital — Jinju
• Chungbuk National University Hospital — Cheongju-si
• Gachon Gil University Medical Center — Incheon
• Korea University Anam Hospital — Seoul
• Seoul National University Hospital — Seoul
• … и ещё 5 центров

Австралия · 4 центра

• Southern Oncology Clinical Research Unit — Adelaide
• Austin Health — Melbourne
• Breast Cancer Research Centre - WA — Perth
• Blacktown Hospital — Sydney

США · 2 центра

• Dana Farber Cancer Institute — Boston
• Vanderbilt Ingram Cancer Center — Nashville

Идентификаторы

NCT: NCT05523947 · YH32367-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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