Study Investigating Safety,Tolerability,Pharmacokinetics and Antitumor Activities of HBM4003 Combine With Toripalimab

Study Overview
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Brief Summary
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HBM4003 in combination with Toripalimab. The expected duration of treatment for each subject will vary according to the number of cycles completed; the number of cycles will depend on whether the subject benefits from the treatment. The study consists of a 4-week screening period, a 21-day treatment cycle (repeatable, depending on the presence/absence of clinical benefit), EOT visit after discontinuation of treatment, and 2 follow-up visits 28 days (± 2 days) and 84 days (± 5 days) after the last study medication.

Detailed Description
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An open-label Phase 1 study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 combined with toripalimab in patients with advanced melanoma and other solid tumors. The study is composed of two part, part 1 will be approximately 31subjects and Part 2 will be approximately 30 subjects.

Official Title
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An Open Phase I Study to Evaluate the Safety, Tolerability, PK / PD, and Initial Efficacy of HBM4003 in Combination With Toripalimab in Patients With Advanced Melanoma and Other Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: HBM4003 and Triprilimab


Participation Criteria
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Eligibility Criteria
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Main inclusion/exclusion criteria: 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. For Part 1 of the study, patients histopathologically diagnosed with advanced or recurrent solid tumors For Part 2 of the study, patients with locally advanced or metastatic melanoma who had been pathologically confirmed and could not be surgically removed were enrolled. Subjects must be able to provide fresh 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. Main exclusion criteria Patients who are simultaneously participating in another clinical study, unless the study is an observational (non-interventional) clinical study or the patient is already in the survival follow-up period of the interventional study. Patients with a history of severe allergic diseases, a history of severe drug allergies, and known or suspected allergy to macromolecular protein preparations or HBM4003 excipients or toripalimab excipients. Previous and concomitant drugs or treatments to be excluded like CTLA4, PD-1,PD-L1. Insufficient recovery from previous treatments: Diseases that may affect the efficacy and safety of the investigational product. A history of other malignant diseases within 5 years before the first dose. Symptomatic, active, or urgent treatment-requiring central nervous system (CNS) metastasis with imaging evidence (based on CT or MRI assessment). Subjects with pleural effusion, pericardial effusion, or ascites Subjects who the investigator believes may have other factors that will affect the efficacy or safety evaluation of this study (e.g., mental disorders, alcoholism, drug use, etc.). Women who are pregnant or breastfeeding, or who plan to become pregnant during the study period and within 3 months after the last administration of the investigational product.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBM4003+Toripalimap<br>HBM4003 combined with toripalimab in patients with advanced melanoma and other solid tumors | Drug: HBM4003 and Triprilimab<br>* Subjects will be treated with HBM4003 on Day 1 Cycle 1 and be treated with HBM4003 and Triprilimab during each 21-day cycles from Cycle 2 in part 1.Subjects will be treated with HBM4003 and Triprilimab on Day 1 during each 21-day cycle in part 2.<br>* Other names: HBM4003;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prat 1 :MTD | The maximum tolerated dose (MTD) of HBM4003 combined with toripalimab | approximate 42 days | 
| Prat 1 :RP2D | Recommended Phase 2 dose (RP2D) of HBM4003 combined with toripalimab | approximate 42 days | 
| Part 1:Number of subjects with DLT in each dose group within 2 cycles (42 days) after the first trial administration | DLT observation period was defined as two treatment cycles with a total of 42 days,including 21 days in the first cycle (HBM4003 single drug treatment cycle) and 21 days in the second cycle (HBM4003 combined with triprilimab treatment cycle). | approximate 42 days | 
| Part 2:ORR | Proportion of patients with complete response (CR) and partial response (PR) | maximum 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1:ORR | Proportion of patients with complete response (CR) and partial response (PR) | maximum 3 years | 
| Part 1:Disease Control Rate，DCR | Including complete response (CR),partial response (PR) and disease stability (SD) | maximum 3 years | 
| Part 1:Duration of Response, DOR | Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason) | maximum 3 years | 
| Part 1:Duration of Disease Control, DDC | 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 3 years | 
| Cmax (Maximum serum concentration) | Cmax | maximum 3 years | 
| Tmax (Time to reach maximum serum concentration) | Tmax | maximum 3 years | 
| AUC0-last | AUC0-last | maximum 3 years | 
| AUC0-tau (Area under the serum concentration versus time curve from time zero to the dosing interval tau | AUC0-tau | maximum 3 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 3 years | 
| Part 2:DCR | Proportion of patients with CR, PR and SD | maximum 3 years | 
| Part 2:DOR | Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason) | maximum 3 years | 
| Part 2:DDC | 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 3 years | 
| Prat 2:OS | The length of time from the beginning of treatment to the death of the subject (for any reason) | maximum 3 years | 
| Part 2:PFS | The length of time from the beginning of treatment to the onset of disease progression or (for any reason) death; | maximum 3 years | 
| Prat 2: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 3 years |