HBM4003 Combine With Toripalimab in Patients With Advanced NEN and Other Solid Tumors Study

NCT05167071 | Active Not Recruiting Phase 1

• 1 other identifier: 4003.6
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

To select RP2D/MTD of HBM4003 in combination with Toripalimab in dose confirmation part(Part 1) and use the RP2D in dose expansion part (Part 2) to evaluate the safety, tolerability, PK/PD and preliminary efficacy of in patients with advanced NEN and other solid tumors

Conditions

Solid Tumors; Neuroendocrine Tumors; CRC

Outcome Measures

Primary Outcomes (4)

• Part 1: DLT

  Number of subjects with DLT in each dose cohort within 1 cycle (21 days) after the first drug administration

  approximate 21 days

• Part 1: MTD

  The maximum tolerated dose (MTD) of HBM4003 combined with Toripalimab

  approximate 21 days

• Part 1: RP2D

  The recommended phase 2 dose (RP2D) of HBM4003 combined with Toripalimab

  approximate 21 days

• Part 2: ORR

  Proportion of subjects with complete response (CR) and partial response (PR)

  maximum 2 years

Study Arms (3)

HBM4003(dose 1) and Toripalimab

EXPERIMENTAL

Arm A: HBM4003(dose 1) combined with Toripalimab in patients with advanced NEN

Drug: HBM4003; Drug: Toripalimab

HBM4003(dose 2) and Toripalimab

EXPERIMENTAL

Arm B: HBM4003(dose 2) combined with Toripalimab in patients with advanced NEN

Drug: HBM4003; Drug: Toripalimab

HBM4003 and Tislelizumab

EXPERIMENTAL

Arm F: HBM4003(dose 1) combined with Tislelizumab in patients with advanced CRC

Drug: HBM4003; Drug: Tislelizumab

Interventions

HBM4003 DRUG

Subjects will be treated with HBM4003 on Day 1 during each 21-day cycle.

Also known as: Porustobart

HBM4003 and Tislelizumab; HBM4003(dose 1) and Toripalimab; HBM4003(dose 2) and Toripalimab

Toripalimab DRUG

Subjects will be treated with Toripalimab on Day 1 during each 21-day cycle.

HBM4003(dose 1) and Toripalimab; HBM4003(dose 2) and Toripalimab

Tislelizumab DRUG

Subjects will be treated with Tislelizumab on Day 1 during each 21-day cycle.

HBM4003 and Tislelizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For arm A and B of Part 2 in the study, Patients with non- functional metastatic neuroendocrine tumor confirmed by histopathology.
• For arm F of Part 2 in the study, Patients with metastatic colorectal adenocarcinoma diagnosed by histopathology.
• Patients must be able to provide archived tumor tissues after latest treatment or fresh tumor tissues and relevant pathology report.
• 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). The lesion had not previously received surgery, radiotherapy and/or local treatment.
• Patients with Eastern Cooperative Oncology Group(ECOG) performance status score ≤1.
• Every woman or man with potential fertility needs to use an effective contraceptive method during the study, up to within 3 months after last drug administration.
• Willing and able to comply with study-specified visits schedule, treatment plan, laboratory examination and other study procedures.

You may not qualify if:

• Patients who are simultaneously participating in another clinical 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 or Toripalimab or Tislelizumab or its excipients.
• Previous and concomitant drugs or treatments to be excluded like:
• Anti-CTLA4 drug;
• For part 1, anti-PD1 anti-PDL1 or anti-PDL2 treatment was received within 8 weeks prior to the start of the study;
• For part 2, patients received anti-PD1, anti-PDL1 or anti-PDL2 treatment during the relapse or metastasis stage, and the time from the last treatment is short than 12 months before the first dose;
• Received other antitumor treatment (including chemotherapy, radiation, targeted therapy, or biotherapy), antitumor vaccine, chinese herbal medicine or proprietary medicine with anti-tumor effect, Immunosuppressant or glucocorticoid, Transfusion of PLT or RBC prior to initiation of study treatment;
• live attenuated vaccine was received before study administration or planned during the study period.
• Insufficient recovery from previous treatments.
• Diseases that may affect the efficacy and safety of the investigational product, including but not limited to active infection, active autoimmune disease or autoimmune disease, primary immunodeficiency disease, any clinically significant cardiovascular disease, severe pulmonary insufficiency, organ transplantation, etc.
• 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 that could not be stabilized by repeated drainage or other methods were determined by investigator.
• 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.).
• 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.

Sponsors & Collaborators

• Harbour BioMed (Guangzhou) Co. Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, China

Location

Related Publications (1)

• Zhang P, Chen K, Yang J, Song L, Zheng F, Luo R, He Y, Li F, Yang D, Cao N, Tao X, Shen L, Lu M. Efficacy and safety of HBM4003 combined with toripalimab in refractory neuroendocrine neoplasms: a multicenter, phase II study. EClinicalMedicine. 2025 Jun 3;84:103249. doi: 10.1016/j.eclinm.2025.103249. eCollection 2025 Jun.

  PMID: 40521168 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

toripalimab; tislelizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Lin Shen, Ph.D

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 22, 2021
• Study Start: December 28, 2021
• Primary Completion: September 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

CN (1)