Clinical trial NCT04727164: Study Investigating Safety,Tolerability,Pharmacokinetics and Antitumor Activities of HBM4003 Combine With Toripalimab
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-01-27
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Main inclusion/exclusion criteria:

Main inclusion criteria

1. 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.
2. For Part 1 of the study, patients histopathologically diagnosed with advanced or recurrent solid tumors
3. 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.
4. Subjects must be able to provide fresh or archived tumor tissues .
5. Patients whose estimated survival time is more than 3 months.
6. Patients with at least one measurable lesion at baseline according to RECIST (Version 1.1).
7. Patients with Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
8. Patients whose organ function must meet the study requirements:
9. Every woman or man with potential fertility needs to use an effective contraceptive method.

Main exclusion criteria

1. 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.
2. 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.
3. Previous and concomitant drugs or treatments to be excluded like CTLA4, PD-1,PD-L1.
4. Insufficient recovery from previous treatments:
5. Diseases that may affect the efficacy and safety of the investigational product.
6. A history of other malignant diseases within 5 years before the first dose.
7. Symptomatic, active, or urgent treatment-requiring central nervous system (CNS) metastasis with imaging evidence (based on CT or MRI assessment).
8. Subjects with pleural effusion, pericardial effusion, or ascites
9. 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.).
10. 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.

Primary outcomes:
measure: Prat 1 :MTD
timeFrame: approximate 42 days
measure: Prat 1 :RP2D
timeFrame: approximate 42 days
measure: Part 1:Number of subjects with DLT in each dose group within 2 cycles (42 days) after the first trial administration
timeFrame: approximate 42 days
measure: Part 2:ORR
timeFrame: maximum 3 years
Secondary outcomes:
measure: Part 1:ORR
timeFrame: maximum 3 years
measure: Part 1:Disease Control Rate，DCR
timeFrame: maximum 3 years
measure: Part 1:Duration of Response, DOR
timeFrame: maximum 3 years
measure: Part 1:Duration of Disease Control, DDC
timeFrame: maximum 3 years
measure: Cmax (Maximum serum concentration)
timeFrame: maximum 3 years
measure: Tmax (Time to reach maximum serum concentration)
timeFrame: maximum 3 years
measure: AUC0-last
timeFrame: maximum 3 years
measure: AUC0-tau (Area under the serum concentration versus time curve from time zero to the dosing interval tau
timeFrame: maximum 3 years
measure: The immunogenicity of HBM4003 and Triprilimab
timeFrame: maximum 3 years
measure: Part 2:DCR
timeFrame: maximum 3 years
measure: Part 2:DOR
timeFrame: maximum 3 years
measure: Part 2:DDC
timeFrame: maximum 3 years
measure: Prat 2:OS
timeFrame: maximum 3 years
measure: Part 2:PFS
timeFrame: maximum 3 years
measure: Prat 2:The immunogenicity of HBM4003 and Triprilimab
timeFrame: maximum 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: JUN GUO, DOCTOR
role: PRINCIPAL_INVESTIGATOR
References: