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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
137
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.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGTreatment-emergent adverse events (TEAEs) up to Day 21
To assess the safety and tolerability of YH32367
Time frame: 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)
Time frame: through dose expansion part completion, approximately 2.5 year
Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
To characterize the PK of YH32367
Time frame: up to 66 weeks
maximum observed serum concentration (Cmax)
To characterize the PK of YH32367
Time frame: up to 66 weeks
time to reach Cmax (Tmax)
To characterize the PK of YH32367
Time frame: 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
Time frame: 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
Time frame: through study completion, approximately 3.5 year
Duration of Response (DoR)
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Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States
RECRUITINGSouthern Oncology Clinical Research Unit
Adelaide, Australia
RECRUITINGAustin Health
Melbourne, Australia
RECRUITINGBreast Cancer Research Centre - WA
Perth, Australia
WITHDRAWNBlacktown Hospital
Sydney, Australia
RECRUITINGCHA Bundang Medical Center
Seongnam-si, Gyeonggi-do, South Korea
RECRUITINGCatholic University of Korea St. Vincent's Hospital
Suwon, Gyeonggi-do, South Korea
RECRUITINGAjou University Hospital
Suwon, Gyeonggi-do, South Korea
RECRUITINGGyeongsang National University Hospital
Jinju, Gyeongsangnam-do, South Korea
RECRUITING...and 9 more locations
To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
Time frame: 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
Time frame: through study completion, approximately 3.5 year
Depth of Response
To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
Time frame: through study completion, approximately 3.5 year
Time to Response
To assess the anti-tumor efficacy according to RECIST v1.1 by Investigator assessment
Time frame: 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
Time frame: through study completion, approximately 3.5 year
TEAEs
To assess the safety and tolerability of YH32367 at the RP2D
Time frame: through dose expansion part completion, approximately 2.5 year
Overall Survival (OS)
To assess overall survival of YH32367
Time frame: through study completion, approximately 3.5 year