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

• ClinicalTrials.gov Identifier: NCT05523947
• Recruitment Status: Recruiting
• First Posted: September 1, 2022
• Last Update Posted: January 23, 2024
• Sponsor: Yuhan Corporation
• Information provided by (Responsible Party): Yuhan Corporation

Tracking Information

• First Submitted Date: August 24, 2022
• First Posted Date: September 1, 2022
• Last Update Posted Date: January 23, 2024
• Actual Study Start Date: August 26, 2022
• Estimated Primary Completion Date: January 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 29, 2022)

• Treatment-emergent adverse events (TEAEs) up to Day 21 [ Time Frame: in dose escalation part, an average of 21 days ]
  To assess the safety and tolerability of YH32367
• Objective Response Rate (ORR) [ Time Frame: through dose expansion part completion, approximately 2.5 year ]
  To assess the ORR of YH32367 at the recommended Phase 2 dose (RP2D) according to RECIST v1.1 by blinded independent central reviews (BICR)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 29, 2022)

• Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast) [ Time Frame: up to 66 weeks ]
  To characterize the PK of YH32367
• maximum observed serum concentration (Cmax) [ Time Frame: up to 66 weeks ]
  To characterize the PK of YH32367
• time to reach Cmax (Tmax) [ Time Frame: up to 66 weeks ]
  To characterize the PK of YH32367
• Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies [ Time Frame: through study completion, approximately 3.5 year ]
  To explore the immunogenicity of YH32367
• Objective Response Rate (ORR) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• Duration of Response (DoR) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• Disease Control Rate (DCR) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• Depth of Response [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• Time to Response [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• Progression-free survival (PFS) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
• TEAEs [ Time Frame: through dose expansion part completion, approximately 2.5 year ]
  To assess the safety and tolerability of YH32367 at the RP2D
• Overall Survival (OS) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess overall survival of YH32367

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 29, 2022)

• Immune ORR (iORR) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the immune-related efficacy according to iRECIST by Investigator assessment
• Immune Duration of Response (iDOR) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the immune-related efficacy according to iRECIST by Investigator assessment
• Immune PFS (iPFS) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the immune-related efficacy according to iRECIST by Investigator assessment
• Soluble 4-1BB (CD137) [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the biomarkers related to YH32367
• HER2, CD4, CD8, CD56, Perforin, FoxP3, PD-L1 [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the biomarkers related to YH32367
• Absolute numbers and relative proportions for immunophenotyping [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the biomarkers related to YH32367
• Cytokines [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the biomarkers related to YH32367
• Changes in receptor occupancy compared to baseline [ Time Frame: through study completion, approximately 3.5 year ]
  To assess the biomarkers related to YH32367

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Clinical Trial of YH32367 in Patients With HER2 Positive Locally Advanced or Metastatic Solid Tumor
• Official Title: A Phase 1/2, Non-randomized, 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
• 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 HER signaling in HER2-expressing tumor cells. YH32367 stimulats IFN-γ secretion from T cells and thereby inducing tumor cells lysis.

This is a Phase 1/2, non-randomized, 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) or the RP2D of YH32367, and a Dose Expansion part, to confirm the safety, tolerability and efficacy of YH32367 at the RP2D.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HER2-Positive Solid Tumor

Intervention

Drug: YH32367

Dose Escalation Part: 8 Cohorts (Dose level: 0.3, 0.75, 1.5, 3, 6, 12, 20, and 30 mg/kg). In Dose Escalation part, approximately 30 patients will be enrolled and patients are assigned to receive YH32367 at a starting dose of 0.3 mg/kg and the dose being escalated/de-escalated in adjacent dose cohorts will be up to 30 mg/kg.

Dose Expansion Part: 2 Cohorts (Cohort 1: Breast cancer, Cohort 2: Gastric cancer). Upon completion of the Dose Escalation part with the determination of MTD/RP2D, the Dose Expansion part will initiate. Dose Expansion part will consist of multiple cohorts in patients who were treated with three or more prior lines of therapy, HER2-positive breast cancer(Cohort 1); in patients who were treated with two or more prior lines of therapy, HER2-positive gastric or gastroesophageal junction adenocarcinoma(Cohort 2). Approximately 40 patients will be enrolled in each cohort. Additional cohorts may be added, taking into account available non-clinical or clinical data.

Study Arms

Experimental: YH32367

Dose Escalation Part: 8 Cohorts (Dose level: 0.3, 0.75, 1.5, 3, 6, 12, 20, and 30 mg/kg). In Dose Escalation part, patients are assigned to receive YH32367 at a starting dose of 0.3 mg/kg and the dose being escalated/de-escalated in adjacent dose cohorts will be 0.75, 1.5, 3, 6, 12, 20, and 30 mg/kg.

Dose Expansion Part: 2 Cohorts (Cohort 1: Breast cancer, Cohort 2: Gastric cancer). Dose Expansion part will consist of multiple cohorts in patients who were treated with three or more prior lines of therapy including at least one trastuzumab-based regimen, HER2-positive, locally advanced or metastatic breast cancer(Cohort 1); in patients who were treated with two or more prior lines of therapy including at least one trastuzumab-based regimen, HER2-positive, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma(Cohort 2).

Intervention: Drug: YH32367

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 29, 2022): 110
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 6, 2026
• Estimated Primary Completion Date: January 31, 2024 (Final data collection date for primary outcome measure)

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 breast cancer
  2. Cohort 2: Pathologically confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jungeun Song; +82-2-828-0713; jsong@yuhan.co.kr

Contact: Jiah Kang; +82-2-828-0020; jiah0213@yuhan.co.kr

• Listed Location Countries: Australia, Korea, Republic of

Administrative Information

• NCT Number: NCT05523947
• Other Study ID Numbers: YH32367-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to andrew90@yuhan.co.kr.

A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Beginning 1 year and ending 5 years after all trial endpoints were assessed
• Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to andrew90@yuhan.co.kr.

• Current Responsible Party: Yuhan Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Yuhan Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sun Young Rha; Severance Hospital
• Principal Investigator: Sung-Bae Kim; Asan Medical Center
• Principal Investigator: Do-Youn Oh; Seoul National University Hospital
• Principal Investigator: Jin Seok Ahn; Samsung Medical Center
• Principal Investigator: Ganessan Kichenadasse; Southern Oncology Clinical Research Unit
• Principal Investigator: Jennifer Man; Blacktown Hospital
• Principal Investigator: Arlene Chan; Breast Cancer Research Centre WA

• PRS Account: Yuhan Corporation
• Verification Date: January 2024