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

HER2-Positive Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05523947
• Other study ID #: YH32367-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 26, 2022
• Est. completion date: December 1, 2026

Study information

• Verified date: June 2024
• Source: Yuhan Corporation
• Contact: SeoYeon So
• Phone: +82-2-828-0405
• Email: syso[@]yuhan.co.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 137
• Est. completion date: December 1, 2026
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HER2-Positive Solid Tumor
• Neoplasms

Intervention

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 65 and 40 patients, respectively.

Locations

Country	Name	City	State
Australia	Southern Oncology Clinical Research Unit	Adelaide
Australia	Austin Health	Melbourne
Australia	Breast Cancer Research Centre - WA	Perth
Australia	Blacktown Hospital	Sydney
Korea, Republic of	CHA Bundang Medical Center	Seongnam	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, St. Mary's hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yuhan Corporation

Countries where clinical trial is conducted

Australia,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immune ORR (iORR)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year
Other	Immune Duration of Response (iDOR)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year
Other	Immune PFS (iPFS)	To assess the immune-related efficacy according to iRECIST by Investigator assessment	through study completion, approximately 3.5 year
Primary	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
Primary	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	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
Secondary	maximum observed serum concentration (Cmax)	To characterize the PK of YH32367	up to 66 weeks
Secondary	time to reach Cmax (Tmax)	To characterize the PK of YH32367	up to 66 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Depth of Response	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Secondary	Time to Response	To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment	through study completion, approximately 3.5 year
Secondary	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
Secondary	TEAEs	To assess the safety and tolerability of YH32367 at the RP2D	through dose expansion part completion, approximately 2.5 year
Secondary	Overall Survival (OS)	To assess overall survival of YH32367	through study completion, approximately 3.5 year