Clinical trial NCT05523947: Clinical Trial of YH32367 in Patients With HER2 Positive Locally Advanced or Metastatic Solid Tumor
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: HER2-Positive Solid Tumor
Keywords: YH32367
HER2/4-1BB bispecific antibody
Solid tumor
Breast cancer
Gastric cancer
HER2-positive
Biliary tract cancer
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2022-09-01
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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-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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-emergent adverse events (TEAEs) up to Day 21
timeFrame: in dose escalation part, an average of 21 days
measure: Objective Response Rate (ORR)
timeFrame: through dose expansion part completion, approximately 2.5 year
Secondary outcomes:
measure: Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: up to 66 weeks
measure: maximum observed serum concentration (Cmax)
timeFrame: up to 66 weeks
measure: time to reach Cmax (Tmax)
timeFrame: up to 66 weeks
measure: Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies
timeFrame: through study completion, approximately 3.5 year
measure: Objective Response Rate (ORR)
timeFrame: through study completion, approximately 3.5 year
measure: Duration of Response (DoR)
timeFrame: through study completion, approximately 3.5 year
measure: Disease Control Rate (DCR)
timeFrame: through study completion, approximately 3.5 year
measure: Depth of Response
timeFrame: through study completion, approximately 3.5 year
measure: Time to Response
timeFrame: through study completion, approximately 3.5 year
measure: Progression-free survival (PFS)
timeFrame: through study completion, approximately 3.5 year
measure: TEAEs
timeFrame: through dose expansion part completion, approximately 2.5 year
measure: Overall Survival (OS)
timeFrame: through study completion, approximately 3.5 year
Other outcomes:
measure: Immune ORR (iORR)
timeFrame: through study completion, approximately 3.5 year
measure: Immune Duration of Response (iDOR)
timeFrame: through study completion, approximately 3.5 year
measure: Immune PFS (iPFS)
timeFrame: through study completion, approximately 3.5 year
Locations:
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
city: Melbourne
country: Australia
facility: Austin Health
city: Perth
country: Australia
facility: Breast Cancer Research Centre - WA
city: Sydney
country: Australia
facility: Blacktown Hospital
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, St. Mary's hospital
Study officials:
affiliation: Severance Hospital
name: Sun Young Rha
role: PRINCIPAL_INVESTIGATOR
affiliation: Asan Medical Center
name: Sung-Bae Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Do-Youn Oh
role: PRINCIPAL_INVESTIGATOR
affiliation: Samsung Medical Center
name: Jin Seok Ahn
role: PRINCIPAL_INVESTIGATOR
affiliation: Southern Oncology Clinical Research Unit
name: Ganessan Kichenadasse
role: PRINCIPAL_INVESTIGATOR
affiliation: Blacktown Hospital
name: Jennifer Man
role: PRINCIPAL_INVESTIGATOR
affiliation: Breast Cancer Research Centre WA
name: Arlene Chan
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Anam Hospital
name: Ju Won Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: The Catholic University of Korea, St. Mary's hospital
name: Myung Ah Lee
role: PRINCIPAL_INVESTIGATOR
affiliation: CHA Bundang Medical Center
name: Hongjae Chon
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Health
name: Niall Tebbutt
role: PRINCIPAL_INVESTIGATOR
References: