An Engineered Sirpα Fused to Anti-Pd-L1 And Tgf-β Fusion Protein (HCB301) in Subjects With Selected Advanced Tumors

A Phase 1, Open-label, Multicenter, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HCB301 in Subjects With Advanced Solid Tumors or Relapsed and Refractory cHL

The purpose of this study is to find out whether IV injection of HCB301 is an effective treatment for different types of advanced solid tumors and relapsed and refractory classical Hodgkin lymphomas and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.

Study Overview

• Status: Recruiting
• Conditions: Refractory Hodgkin Lymphoma; Advanced Solid Tumor
• Intervention / Treatment: Drug: HCB301

Detailed Description

This is a phase 1, open-label, multicenter, dose-escalation study. This study is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and identification of maximum tolerated dose (MTD) of HCB301 intravenous injection in adults with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.

Eligible subjects must have failed standard therapies, been intolerable, or been considered medically inappropriate by the investigator. Subjects will be treated until unacceptable AEs, radiographic or clinical documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: FBD Clinical; Phone Number: +886-2-27921366; Email: HCB301-101@hanchorbio.com

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Contact: Dr. Tong; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
  • Hangzhou, China
    • Recruiting
    • Zhejiang Provincial Cancer Hospital
    • Contact: Dr. Zhu; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
  • Xuzhou, China
    • Recruiting
    • Xuzhou Central Hospital
    • Contact: Dr. Sun; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
  • Yantai, China
    • Recruiting
    • Yantai Yuhuangding Hospital
    • Contact: Dr. Liu; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
  • Zhujiang, China
    • Recruiting
    • Southern Medical University Zhujiang Hospital
    • Contact: Dr. Hu; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
• Taiwan
  • Kaohsiung City, Taiwan
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Contact: Li-Tzong Chen, MD; Phone Number: +886-2-27921366; Email: hcb301-101@hanchorbio.com
• United States
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health-Upstate

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and be willing to sign the ICF.
2. Male and female subjects of ≥18 years of age.

3. Histologically/cytologically confirmed, locally advanced solid tumor:

   subjects confirmed advanced solid tumors who have relapsed or refractory and should have no options for standard or approved therapies known to potentially confer clinical benefit or classical Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of systemic therapy.

4. For subjects with advanced solid tumors - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
5. For subjects with classical Hodgkin lymphoma - must have classical Hodgkin lymphoma that is measurable or assessable for response.
6. Must have ECOG performance status of 0 to 1 at Screening.
7. Able to provide tumor tissue samples.
8. Have a life expectancy of ≥12 weeks.

Exclusion Criteria:

1. With known history of hypersensitivity to any components of HCB301.
2. Known active or untreated CNS metastases and/or carcinomatous meningitis.
3. Have undergone a major surgery or radical radiotherapy within 28 days or palliative radiotherapy within 14 days or have used a radioactive drug within 56 days prior to the first dose of HCB301.
4. Clinically significant cardiovascular condition.
5. Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
6. With known inherited or acquired bleeding disorder or bleeding diathesis. .
7. Have RBC transfusion within 4 weeks prior to Screening.
8. With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
9. Any investigational or approved systemic cancer therapy administered within 21 days or 5 half-lives, whichever is shorter, before the first dose of the study drug.
10. Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 100 mg/QD.
11. Have used herbal medication within 14 days prior to the first dose of HCB301.
12. Have received any treatment targeting the SIRPα-CD47, PD-L1, or TGF-β pathway.
13. Have other malignancies requiring treatment within 2 years prior to the first dose of HCB301.
14. An investigational device used within 28 days prior to the first dose of HCB301.
15. Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
16. Known to have a history of alcoholism or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: 0.3 mg/kg HCB301; 0.3 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 0.6 mg/kg HCB301; 0.6 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 1.2 mg/kg HCB301; 1.2 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 2.4 mg/kg HCB301; 2.4 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 4.8 mg/kg HCB301; 4.8 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 9.6 mg/kg HCB301; 9.6 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors
Experimental: Experimental: 15.0 mg/kg HCB301; 15.0 mg/kg HCB301 in subjects with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.	Drug: HCB301; HCB301 administered via. intravenous (IV) infusion.; Other Names: 2023-3979 Solid Tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/incidence and percentage of subjects with adverse events, including ADA.	To evaluate the safety and tolerability of HCB301.	12 months
Number of subjects with MTD and RDE of HCB301.	To determine the MTD and RDE.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Defined as the duration from the start of treatment until tumor progression or death of any cause.	12 months
Overall Rate Response (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or critical response (CR).	12 months
Duration of Response (DoR)	DoR is defined as time from date of initial documentation of a response (PR or CR) to date of first documented evidence of progressive disease (PD).	12 months
Disease Control Rate (DCR)	DCR is defined as the proportion of participants who have a partial response (PR), critical response (CR), or disease stable (SD).	12 months
Peak Plasma Concentration (Cmax) of HCB301	Peak Plasma Concentration (Cmax) of HCB301 following single and repeated IV doses of HCB301 at different dose levels.	12 months
Area under the plasma concentration versus time curve (AUC) of HCB301	Area under the plasma concentration versus time curve (AUC) of HCB301 following single and repeated IV doses of HCB301 at different dose levels.	12 months
Time to maximum drug concentration in plasma (Tmax) of HCB301	Time to maximum drug concentration in plasma (Tmax) of HCB301 following single and repeated IV doses of HCB301 at different dose levels.	12 months
Terminal elimination half-life (t1/2) of HCB301	Terminal elimination half-life (t1/2) of HCB301 following single and repeated IV doses of HCB301 at different dose levels.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD47 receptor occupancy on circulating red blood cells (RBCs)	CD47 receptor occupancy on circulating red blood cells (RBCs) will be measured as an indication of target engagement.	12 months
ctDNA detection	ctDNA detection in participants using next-generation sequencing (NGS ).	12 months
Concentration of potential PD biomarkers in participants will be assess.	Changes in CD47 receptor occupancy on circulating CD3+ T cells and TGFβ1, 2, 3 will be assessed after HCB301 treatment.	12 months

Collaborators and Investigators

• Sponsor: FBD Biologics Limited
• Collaborators: HanchorBio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Immunotherapy; PD-L1; Tumor; CD47; TGF-beta
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Osteochondrodysplasias; Bone Diseases, Developmental; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Neoplasms; Hodgkin Disease; Camurati-Engelmann Syndrome
• Other Study ID Numbers: HCB301-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No