A Study to Evaluate Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 Combine With Toripalimab in Patients With Advanced HCC and Other Solid Tumors

An Open-Label, Phase 1 Clinical Study 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

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.

Study Overview

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

Detailed Description

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 :

• A screening period: 28 days
• A treatment period:
• Part 1 dose confirmation study
• Part 2 dose expansion study
• A post-treatment follow-up period, including
• A safety follow-up period: 28 days after the last dose of study drug;
• Post-treatment follow-up visit: day 84 after the last dose of study drug;
• Survival follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 67
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoying Wang; Phone Number: +18201936643; Email: hbm4003public@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 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. 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.

3. 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.

   1. Cohort 1: Patients with advanced HCC who have not received previous treatment with anti-PD-1 pathway drugs (including anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs), including patients who have received or have not received systemic treatment (e.g. anti-VEGF/VEGFR monoclonal antibodies, anti-VEGFR-TKIs, chemotherapy); patients who have received adjuvant/neoadjuvant therapy with anti-PD-1 pathway drugs and have disease progression more than 12 months after the end of treatment can be enrolled into this cohort
   2. Cohort 2: advanced HCC patients who have progressed during or after anti-PD-1 pathway drug therapy (with clearly documented radiographic evidence of progression), including patients who have or have not received systemic therapy (e.g., anti-VEGF/VEGFR monoclonal antibodies, anti-VEGFR-TKIs, chemotherapy); patients who have progressed within 6 months after the end of adjuvant/neoadjuvant therapy with anti-PD-1 pathway drugs may be enrolled into this cohort
   3. Other possible tumor expansion cohorts will be further revised as more data become available.
4. Patients must be able to provide fresh tumor tissues 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.
10. Willing and able to comply with study-specified visits schedule, treatment plan, laboratory examination and other study procedures.

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. For the liver cancer cohort in Part 2 of the study, patients with pathological findings suggestive of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or mixed hepatocellular carcinoma-cholangiocarcinoma were excluded.
4. Previous and concomitant drugs or treatments to be excluded like CTLA4, PD-1,PD-L1.
5. Insufficient recovery from previous treatments
6. Diseases that may affect the efficacy and safety of the investigational product.
7. A history of other malignant diseases within 5 years before the first dose.
8. Symptomatic, active, or urgent treatment-requiring central nervous system (CNS) metastasis with imaging evidence (based on CT or MRI assessment).
9. Subjects with pleural effusion, pericardial effusion, or ascites
10. Patients with severe liver cirrhosis, liver atrophy or hypertension.
11. Imaging revealed that the main portal vein tumor thrombus was more than 1/2, and the vein tumor thrombus or heart was involved.
12. Grade ≥ 2 hepatic encephalopathy within 12 months, or currently requiring medication to prevent or control hepatic encephalopathy.
13. Patients 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.).
14. 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBM4003+Toripalimap; HBM4003 combined with toripalimab in patients with advanced HCC and other solid tumors	Drug: HBM4003 and Triprilimab; Subjects will be treated with HBM4003 and Toripalimap on Day 1 during each 21-day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
• Investigators: Principal Investigator: Jihui Hao, Doctor, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 20, 2021
• Primary Completion (Anticipated): May 30, 2024
• Study Completion (Anticipated): May 30, 2024

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2021
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 4003.5

Drug and device information, study documents

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