HCB101 for Cancer

Recruiting at 7 trial locations

Overseen By FBD Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: FBD Biologics Limited

Must not be taking: Vitamin K antagonists, Herbal medications

Disqualifiers: CNS metastases, Cardiovascular condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of HCB101, administered through an IV, in treating various advanced solid tumors and certain types of non-Hodgkin lymphoma that haven't responded to other treatments. Researchers also seek to identify potential side effects. Individuals with advanced solid tumors or resistant non-Hodgkin lymphoma, especially those who have tried at least two other treatments without success, may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use herbal medications within 14 days before starting the trial. Also, if you are on a vitamin K antagonist like warfarin, you may need to switch to another type of blood thinner.

Is there any evidence suggesting that HCB101 is likely to be safe for humans?

Research has shown that HCB101 was safe in earlier studies. Patients with advanced cancer who had undergone multiple treatments tolerated it well. Early results suggest that the side effects were manageable, and the drug's effects became predictable with increasing doses. Thus far, HCB101 appears safe for humans. However, as this is a Phase 1 trial, the primary goal remains to learn more about its safety and any potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

HCB101 is unique because it targets advanced solid tumors and relapsed or refractory non-Hodgkin lymphoma with a potentially new mechanism of action. Unlike standard treatments like chemotherapy or immunotherapy, which are more generalized, HCB101 is being tested at various dosage levels to specifically hone in on these challenging cancer types. Researchers are excited because this approach may offer a more precise and personalized treatment option, potentially leading to better outcomes for patients with these difficult-to-treat cancers.

What evidence suggests that HCB101 might be an effective treatment for advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma?

Research has shown that HCB101 might help treat advanced solid tumors and relapsed non-Hodgkin lymphoma. HCB101 changes the tumor environment by increasing certain immune cells that may slow or stop tumor growth. Early studies suggest it might help fight cancer cells. Additionally, HCB101 blocks signals that aid tumor growth. While there is hope, further research is needed to confirm its effectiveness. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors or non-Hodgkin lymphoma that's resistant to standard treatments. Participants must have measurable disease, be in fair health (ECOG 0-2), and able to provide tissue samples. They should not have had recent major surgery, untreated side effects from past treatments (except hair loss/anemia), blood transfusions within the last month, or certain other medical conditions.

Inclusion Criteria

Able to understand and willing to sign the ICF

I can provide samples of my tumor for testing.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101

I am currently receiving or have received a cancer treatment that is experimental or approved.

I haven't needed treatment for another cancer within the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HCB101 intravenous injection in a dose-escalation manner to evaluate safety, tolerability, pharmacokinetics, and anti-tumor activity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HCB101

Trial Overview The study tests HCB101, an IV drug targeting the SIRPα-CD47 pathway in patients with various advanced solid tumors or relapsed/refractory non-Hodgkin lymphoma. The goal is to determine its effectiveness and safety profile.

How Is the Trial Designed?

Group I: HCB101 Experimental Treatment 1 Intervention

HCB101 in subjects with advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma. Dosage levels: 0.08 mg/kg, 0.16 mg/kg, 0.32 mg/kg, 0.64 mg/kg, 1.28 mg/kg, 2.56 mg/kg, and 5.12 mg/kg sequentially.

HCB101 is already approved in United States for the following indications:

Approved in United States as HCB101 for:

• Advanced solid tumors
• Relapsed and refractory non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

FBD Biologics Limited

Lead Sponsor

Trials

3

Recruited

260+

Published Research Related to This Trial

The engineered anti-SIRPα monoclonal antibody 1H9 effectively blocks the CD47/SIRPα interaction, enhancing macrophage-mediated phagocytosis of cancer cells and showing promise in promoting tumor cell destruction in preclinical models.

1H9 is well tolerated in nonhuman primates with no adverse effects, suggesting it could be a safe and effective addition to cancer therapies when combined with other tumor-targeting antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting macrophage checkpoint inhibitor SIRPα for anticancer therapy. Liu, J., Xavy, S., Mihardja, S., et al.[2021]

The humanized version of the antibody fragment, (HAb18-huscFv)(2)-Fc, shows reduced immunogenicity compared to the original murine antibody, making it potentially safer for patients with hepatocellular carcinoma (HCC).

This humanized antibody retains strong binding activity and enhances cytotoxic functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), suggesting it could be a more effective treatment option for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity. Zhu, H., Yang, B., Yang, X., et al.[2020]

A novel method was developed to produce refined, functional, tag-free bi-specific diabodies from IgG-like antibodies, enhancing their potential for cancer immunotherapy.

The tag-free bi-specific diabody (hEx3-Db) demonstrated greater effectiveness in inhibiting cancer growth compared to affinity-tagged versions, suggesting improved therapeutic efficacy and potential for industrial-scale production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of the Fc fusion format to generate tag-free bi-specific diabodies. Asano, R., Ikoma, K., Kawaguchi, H., et al.[2010]

Novel variants of therapeutic antibodies with specific amino acid substitutions in the Fc region can completely eliminate binding to Fc gamma receptors (FcγR) and C1q, reducing the risk of unwanted inflammatory responses.

These variants maintain important properties such as binding to FcRn, manufacturability, stability, and low potential for immunogenicity, suggesting they could enhance the safety and efficacy of therapeutic antibodies and fusion proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-engineered antibodies with immune effector functions completely abolished. Wilkinson, I., Anderson, S., Fry, J., et al.[2022]

The TKKTLRT-SIRPαFc conjugate enhances tumor targeting by binding specifically to collagen in tumor tissues, leading to improved accumulation in tumors compared to unmodified SIRPαFc.

In a mouse model of non-small cell lung cancer (NSCLC), the CBD-SIRPαFc conjugate demonstrated more effective and stable antitumor efficacy, increasing the presence of immune-activating macrophages in tumors while potentially reducing side effects on normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A SIRPαFc Fusion Protein Conjugated With the Collagen-Binding Domain for Targeted Immunotherapy of Non-Small Cell Lung Cancer. Liu, J., Meng, Z., Xu, T., et al.[2022]

Genexine developed a novel hybrid Fc (hyFc) technology that enhances the delivery and effectiveness of agonistic protein drugs, such as erythropoietin (EPO), without causing cell death.

The EPO-hyFc demonstrated superior bioactivity compared to traditional EPO formulations in both laboratory and animal studies, and it is currently being tested in a Phase I clinical trial in Korea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-acting erythropoietin fused with noncytolytic human Fc for the treatment of anemia. Yang, SH., Yang, SI., Chung, YK.[2018]

Recombinant immunoglobulins with two Fab' fragments effectively trigger antibody-dependent cellular cytotoxicity, similar to intact IgG antibodies, indicating their potential as effective therapeutic agents.

Immunoglobulins with a single Fab' fragment were found to be inactive, suggesting that the presence of two Fab' fragments is crucial for binding to cell receptors and activating immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Fab-Fc recombinant antibodies for studying the mechanism of triggering the effector activities of immunoglobulins. Uracz, W., Bobrzecka, K., Konieczny, L., et al.[2019]

DSP107, a bispecific fusion protein, effectively enhances immune responses against Diffuse Large B Cell Lymphoma (DLBCL) by blocking the CD47:SIRPα signaling pathway and activating T cells, showing significant tumor reduction in mouse models.

In combination with rituximab, DSP107 increased phagocytosis and T cell cytotoxicity against DLBCL cells, achieving up to 85% reduction in cancer cell numbers in vitro, while demonstrating an excellent safety profile in cynomolgus monkeys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity. Cendrowicz, E., Jacob, L., Greenwald, S., et al.[2022]

AL008 is a novel antibody that targets the SIRPα pathway, enhancing the immune system's ability to engulf tumor cells and promoting antitumor immunity, showing significant efficacy in reducing tumor growth in humanized mouse models.

Unlike traditional SIRPα antibodies that block ligands, AL008 not only degrades SIRPα but also activates myeloid cells, leading to increased T cell proliferation and improved responses when combined with other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AL008 Enhances Myeloid Antitumor Function by Inhibiting SIRPα Signaling and Activating Fc Receptors. Yang, J., Deresa, I., Ho, WH., et al.[2023]

The oncolytic adenovirus Ad-Cab FT, designed to enhance immune response against PD-L1, showed improved tumor-killing efficacy at lower concentrations compared to its predecessor Ad-Cab, thanks to enhanced activation of natural killer (NK) cells.

Ad-Cab FT demonstrated targeted delivery within the tumor microenvironment with minimal leakage to the bloodstream and other organs, suggesting a safer profile for potential clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses. Hamdan, F., Feodoroff, M., Russo, S., et al.[2023]

The study developed a unique human-engineered domain (HED) that effectively binds to the human IgG1 antibody, demonstrating potential for therapeutic applications.

When combined with an antibody fragment and murine IFN-γ, the HED showed significant antitumor efficacy in a mouse model of human breast cancer, indicating its potential as a novel treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HED, a Human-Engineered Domain, Confers a Unique Fc-Binding Activity to Produce a New Class of Humanized Antibody-like Molecules. Zhu, Z., Goel, PN., Zheng, C., et al.[2023]

FS102 is a novel HER2-specific Fc fragment that effectively binds to HER2 and induces significant internalization and degradation of the protein, leading to tumor cell death, particularly in tumors with high HER2 expression.

In patient-derived xenograft models, FS102 demonstrated superior antitumor activity compared to trastuzumab and the combination of trastuzumab and pertuzumab, especially in tumors with a HER2 gene copy number of 10 or more, suggesting its potential as a more effective treatment for HER2-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis. Leung, KM., Batey, S., Rowlands, R., et al.[2018]

Fcabs, like H10-03-6, are a new class of immunotherapeutics that effectively bind to tumor antigens and trigger immune responses, specifically antibody-dependent cytotoxicity (ADCC), to kill cancer cells.

In mouse models, Fcab H10-03-6 significantly slowed the growth of tumors overexpressing Her-2/neu, suggesting its potential as an effective treatment option for cancers with this marker, while showing a different mechanism of action compared to the existing drug trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro activity of an immunoglobulin Fc fragment (Fcab) with engineered Her-2/neu binding sites. Woisetschläger, M., Antes, B., Borrowdale, R., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05892718

NCT05892718 | A Safety and Efficacy Study of HCB101, Fc ... The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548202/

HCB101: a novel potent ligand-trap Fc-fusion protein ... Additionally, HCB101 treatment increased the M1/M2 macrophage ratio in the tumor microenvironment, suggesting repolarization of tumor-associated ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2584

Phase 1 trial of HCB101, a novel Fc-based anti-SIRPα- ... This Phase 1, open-label, dose-escalation trial evaluates HCB101's safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity ...

4. biospace.com biospace.com/press-releases/hanchorbio-presents-phase-1-hcb101-clinical-results-at-faco-2025-demonstrating-safety-and-early-antitumor-activity

HanchorBio Presents Phase 1 HCB101 Clinical Results at ... HCB101-101 is an ongoing multi-national, multi-center, open-label, dose-finding Phase 1 study evaluating HCB101 in adults with advanced solid ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05892718

A Safety and Efficacy Study of HCB101, Fc-fusion Protein ... The trial aims to evaluate the safety, tolerability, pharmacodynamics, and anti-tumor activity of HCB101 in patients with advanced solid tumors.

6. fidelity.com fidelity.com/news/article/default/202510231930PR_NEWS_USPR_____HK05381

HanchorBio Presents Phase 1 HCB101 Clinical Results at ... Early data demonstrate a favorable safety profile, dose-proportional pharmacokinetics, high-level CD47 receptor occupancy, and confirmed partial ...