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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: HBM4003 and Triprilimab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 61
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wangnan ZHOU, Master; Phone Number: +13810905733; Email: wangnan.zhou@harbourbiomed.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HBM4003+Toripalimap; HBM4003 combined with toripalimab in patients with advanced melanoma and other solid tumors	Drug: HBM4003 and Triprilimab; 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.; Other Names: HBM4003

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
• Investigators: Principal Investigator: JUN GUO, DOCTOR, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 28, 2021
• Primary Completion (ANTICIPATED): November 1, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (ACTUAL): January 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 4003.2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No