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: August 16, 2023
• Sponsor: Yuhan Corporation
• Information provided by (Responsible Party): Yuhan Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HER2-Positive Solid Tumor	Drug: YH32367	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 110 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 26, 2022
• Estimated Primary Completion Date: January 31, 2024
• Estimated Study Completion Date: October 6, 2026

Arms and Interventions

Arm

Intervention/treatment

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).

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.

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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)

Secondary Outcome Measures :

1. 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
2. maximum observed serum concentration (Cmax) [ Time Frame: up to 66 weeks ]
   To characterize the PK of YH32367
3. time to reach Cmax (Tmax) [ Time Frame: up to 66 weeks ]
   To characterize the PK of YH32367
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. TEAEs [ Time Frame: through dose expansion part completion, approximately 2.5 year ]
    To assess the safety and tolerability of YH32367 at the RP2D
12. Overall Survival (OS) [ Time Frame: through study completion, approximately 3.5 year ]
    To assess overall survival of YH32367

Other Outcome Measures:

1. Immune ORR (iORR) [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the immune-related efficacy according to iRECIST by Investigator assessment
2. 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
3. Immune PFS (iPFS) [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the immune-related efficacy according to iRECIST by Investigator assessment
4. Soluble 4-1BB (CD137) [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the biomarkers related to YH32367
5. HER2, CD4, CD8, CD56, Perforin, FoxP3, PD-L1 [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the biomarkers related to YH32367
6. Absolute numbers and relative proportions for immunophenotyping [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the biomarkers related to YH32367
7. Cytokines [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the biomarkers related to YH32367
8. Changes in receptor occupancy compared to baseline [ Time Frame: through study completion, approximately 3.5 year ]
   To assess the biomarkers related to YH32367

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

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

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

Locations

Australia

Southern Oncology Clinical Research Unit; Recruiting

Adelaide, Australia

Breast Cancer Research Centre - WA; Recruiting

Perth, Australia

Blacktown Hospital; Recruiting

Sydney, Australia

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Severance Hospital, Yonsei University Health System; Recruiting

Seoul, Korea, Republic of, 03722

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 05505

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

Sponsors and Collaborators

Yuhan Corporation

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

More Information

• Responsible Party: Yuhan Corporation
• ClinicalTrials.gov Identifier: NCT05523947
• Other Study ID Numbers: YH32367-101
• First Posted: September 1, 2022
• Last Update Posted: August 16, 2023
• Last Verified: August 2023

Individual Participant Data (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; Statistical Analysis Plan (SAP); 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.

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

Keywords provided by Yuhan Corporation:

YH32367; HER2/4-1BB bispecific antibody; Solid tumor; Breast cancer; Gastric cancer; HER2-positive

Additional relevant MeSH terms:

Neoplasms