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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| YH32367 | Experimental | Dose Escalation Part: 8 Cohorts. In Dose Escalation part, patients are assigned to receive YH32367 at a starting dose and the dose being escalated/de-escalated in adjacent dose cohorts. Dose Expansion Part: 2 Cohorts (Cohort 1: Biliary tract cancer, Cohort 2: Solid tumors). Dose Expansion 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YH32367 | Drug | 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 approximately 75 and 40 patients, respectively. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| maximum observed serum concentration (Cmax) |
| Measure | Description | Time Frame |
|---|---|---|
| Immune ORR (iORR) | To assess the immune-related efficacy according to iRECIST by Investigator assessment | through study completion, approximately 3.5 year |
| Immune Duration of Response (iDOR) | To assess the immune-related efficacy according to iRECIST by Investigator assessment |
Inclusion Criteria:
[Dose Escalation Part]
[Dose Expansion Part]
Patients who have at least one measurable lesion
Mandatory provision of tumor tissue sample
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operation Team 1 | Contact | +82-2-828-0065 | clinicaltrials@yuhan.co.kr | |
| Heayeon Yoo | Contact | +82-2-828-0065 | hy1221@yuhan.co.kr |
| Name | Affiliation | Role |
|---|---|---|
| Hyejin Choi | Severance Hospital | Principal Investigator |
| Kyu-pyo Kim | Asan Medical Center | Principal Investigator |
| Do-Youn Oh |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States | |
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.
Beginning 1 year and ending 5 years after all trial 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.
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|
To characterize the PK of YH32367
| up to 66 weeks |
| time to reach Cmax (Tmax) | To characterize the PK of YH32367 | up to 66 weeks |
| 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 |
| 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 |
| 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 |
| 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 |
| Depth of Response | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment | through study completion, approximately 3.5 year |
| Time to Response | To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment | through study completion, approximately 3.5 year |
| 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 |
| TEAEs | To assess the safety and tolerability of YH32367 at the RP2D | through dose expansion part completion, approximately 2.5 year |
| Overall Survival (OS) | To assess overall survival of YH32367 | through study completion, approximately 3.5 year |
| through study completion, approximately 3.5 year |
| Immune PFS (iPFS) | To assess the immune-related efficacy according to iRECIST by Investigator assessment | through study completion, approximately 3.5 year |
| Seoul National University Hospital |
| Principal Investigator |
| Joon Oh Park | 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 | Principal Investigator |
| Ju Won Kim | Korea University Anam Hospital | Principal Investigator |
| Myung Ah Lee | The Catholic University of Korea, St. Mary's hospital | Principal Investigator |
| Hongjae Chon | CHA Bundang Medical Center | Principal Investigator |
| Niall Tebbutt | Austin Health | Principal Investigator |
| Jung Hun Kang | Gyeongsang National University Hospital | Principal Investigator |
| Seok Yun Kang | Ajou University School of Medicine | Principal Investigator |
| Hyung Soon Park | Catholic University of Korea St. Vincent's Hospital | Principal Investigator |
| Ji Hong Bae | Gachon Gil University Medical Center | Principal Investigator |
| Cheol Kyung Sin | Ulsan University Hospital | Principal Investigator |
| Hae Seong Park | Dana-Farber Cancer Institute | Principal Investigator |
| Thatcher Heumman | Vanderbilt-Ingram Cancer Center | Principal Investigator |
| Hongsik Kim | Chungbuk National University Hospital | Principal Investigator |
| Vanderbilt Ingram Cancer Center |
| Recruiting |
| Nashville |
| Tennessee |
| 37232 |
| United States |
| Southern Oncology Clinical Research Unit | Terminated | Adelaide | Australia |
| Austin Health | Recruiting | Melbourne | Australia |
| Breast Cancer Research Centre - WA | Withdrawn | Perth | Australia |
| Blacktown Hospital | Recruiting | Sydney | Australia |
| CHA Bundang Medical Center | Recruiting | Seongnam-si | Gyeonggi-do | 13496 | South Korea |
| Catholic University of Korea St. Vincent's Hospital | Recruiting | Suwon | Gyeonggi-do | 16247 | South Korea |
| Ajou University Hospital | Recruiting | Suwon | Gyeonggi-do | 16499 | South Korea |
| Gyeongsang National University Hospital | Recruiting | Jinju | Gyeongsangnam-do | 52727 | South Korea |
| Chungbuk National University Hospital | Recruiting | Cheongju-si | North Chungcheong | 28644 | South Korea |
| Gachon Gil University Medical Center | Recruiting | Incheon | 21565 | South Korea |
| Korea University Anam Hospital | Recruiting | Seoul | 02841 | South Korea |
| Seoul National University Hospital | Recruiting | Seoul | 03080 | South Korea |
| Severance Hospital, Yonsei University Health System | Recruiting | Seoul | 03722 | South Korea |
| Asan Medical Center | Recruiting | Seoul | 05505 | South Korea |
| Samsung Medical Center | Recruiting | Seoul | 06351 | South Korea |
| The Catholic University of Korea, St. Mary's hospital | Recruiting | Seoul | 06591 | South Korea |
| Ulsan University Hospital | Recruiting | Ulsan | 44437 | South Korea |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D013274 | Stomach Neoplasms |
| D001661 | Biliary Tract Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D001660 | Biliary Tract Diseases |
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