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This is an open-label, multi-center phase 1 study. The trial, consisting of Part
1 dose confirmation and Part 2 dose expansion, is designed to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with Toripalimab in patients with advanced HCC and other solid tumors.
subjects will be treated with HBM4003 in combination with Toripalimab for up to 2 years or until confirmed disease progression, unacceptable tolerability or treatment discontinuation through withdrawal of consent occurs, whichever happens first.
This trial consists of :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HBM4003+Toripalimap | Experimental | HBM4003 combined with toripalimab in patients with advanced HCC and other solid tumors |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HBM4003 and Triprilimab | Drug | Subjects will be treated with HBM4003 and Toripalimap on Day 1 during each 21-day cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part1:Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration | Number of subjects who experience DLT events | approximate 21 days |
| Part1:The maximum tolerated dose (MTD) of HBM4003 combined with toripalimab | approximate 21 days | |
| Part1:Recommended Phase 2 dose (RP2D) of HBM4003 combined with toripalimab | approximate 21 days | |
| Part2:ORR, as determined by the Investigator using RECIST 1.1 | Proportion of subjects with complete response (CR) and partial response (PR) | maximum 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1:ORR, as determined by the Investigator using RECIST 1.1 for solid tumors, using RECIST 1.1 and mRECIST for HCC | Proportion of patients with complete response (CR) and partial response (PR) | maximum 2 years] |
| Part 1: Disease Control Rate, DCR, as determined by the Investigator using RECIST 1.1 for solid tumors, using RECIST 1.1 and mRECIST for HCC |
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Main inclusion criteria :
Males or females aged ≥ 18 years at the time of signing the informed consent form. For Part 1 of this study, the subjects should be ≤ 75 years of age.
Patients for Part 1: patients histopathologically diagnosed with advanced or recurrent solid tumors or more line SOC failure or progression within 6m after adjuvant or neoadjuvant therapy.
For Part 2 of the study, patients with histopathologically confirmed advanced hepatocellular carcinoma; Barcelona Clinic Liver Cancer (BCLC) stage C or B; where stage B patients must be unsuitable for surgical and/or local therapy, or have progressive disease after surgical and/or local therapy, or refuse surgical and local therapy.
Patients must be able to provide fresh tumor tissues or archived tumor tissues.
Patients whose estimated survival time is more than 3 months.
Patients with at least one measurable lesion at baseline according to RECIST (Version 1.1).
Patients with Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
Patients whose organ function must meet the study requirements:
Every woman or man with potential fertility needs to use an effective contraceptive method.
Willing and able to comply with study-specified visits schedule, treatment plan, laboratory examination and other study procedures.
Main exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiaoying Wang | Contact | +18201936643 | hbm4003public@harbourbiomed.com | |
| Peter Zhao | Contact | +8617601647910 | peter.zhao@harbourbiomed.com |
| Name | Affiliation | Role |
|---|---|---|
| Jihui Hao, Doctor | Tianjin Medical University Cancer Institute and Hospital | Principal Investigator |
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including proportion of subjects with complete response (CR) and partial response (PR) and stable disease (SD) |
| maximum 2 years |
| Part 1: Duration of Response, DOR, as determined by the Investigator using RECIST 1.1 for solid tumors, using RECIST 1.1 and mRECIST for HCC | Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason) | maximum 2 years |
| Part 1: Duration of Disease Control, DDC, as determined by the Investigator using RECIST 1.1 for solid tumors, using RECIST 1.1 and mRECIST for HCC | For subjects with Cr, PR or SD, the duration from the time of initial administration to the date of disease progression or death (for any reason) was calculated | maximum 2 years |
| Part2: ORR, as determined by the Investigator using mRECIST for HCC | Proportion of patients with complete response (CR) and partial response (PR) | maximum 2 years |
| Part 2: Disease Control Rate, DCR, as determined by the Investigator using RECIST 1.1 and mRECIST for HCC | including proportion of subjects with complete response (CR) and partial response (PR) and stable disease (SD) | maximum 2 years |
| Part2: Duration of Response, DOR, as determined by the Investigator using RECIST 1.1 and mRECIST for HCC | Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason) | maximum 2 years |
| Part2:Duration of Disease Control, DDC, as determined by the Investigator using RECIST 1.1 and mRECIST for HCC | For subjects with Cr, PR or SD, the duration from the time of initial administration to the date of disease progression or death (for any reason) was calculated | maximum 2 years |
| Cmax | Peak Plasma Concentration | maximum 2 years |
| Tmax | Time to reach maximum serum concentration | maximum 2 years |
| AUC0-last | Area under the plasma concentration versus time curve from time zero to last | maximum 2 years |
| AUC0-tau | Area under the serum concentration versus time curve from time zero to the dosing interval tau | maximum 2 years |
| The immunogenicity of HBM4003 and Triprilimab | Including the incidence of ADA positive. For ADA positive patients, the incidence of neutralizing antibody (NAB) was analyzed. | maximum 2 years |
| Part 2: Overall survival (OS) | the length of time from the start of treatment to the death of the subject (for any reason) | maximum 2 years |
| Part 2: Progression-free survival (PFS) | the length of time from the beginning of treatment to the beginning of disease progression or death (for any reason) | maximum 2 years |