HCB101 for Cancer

Recruiting at 6 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

Trial Summary

What is the purpose of this trial?

This trial is testing an IV drug called HCB101 in adults with advanced cancers or certain types of lymphoma that haven't responded to other treatments. The goal is to see if HCB101 can help shrink tumors and to find the safest and most effective dose. Researchers will also monitor for any side effects.

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.

What evidence supports the effectiveness of the drug HCB101 for cancer treatment?

Research on similar treatments, like the SIRPαFc fusion protein, shows it can help the immune system fight cancer by blocking signals that protect tumor cells. This approach has shown promise in enhancing antitumor responses in various cancers, suggesting potential effectiveness for HCB101. ^{1 2 3 4 5}

What safety data exists for HCB101 or similar treatments?

The research on similar treatments shows that the Fc fusion peptide used in cancer therapy demonstrated targeted release in tumors with minimal leakage to other parts of the body in mice, suggesting it is safe for further clinical investigation. ^{6 7 8 9 10}

What makes the drug HCB101 unique for cancer treatment?

HCB101 is a SIRP-alpha-Fc fusion protein that targets the CD47-SIRPα pathway, a key immune checkpoint in cancer, to enhance the body's immune response against tumors. This drug is unique because it combines the ability to block the immunosuppressive signal with a fusion protein that can potentially improve targeting and reduce side effects compared to other treatments. ^{3 4 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A SIRPαFc Fusion Protein Conjugated With the Collagen-Binding Domain for Targeted Immunotherapy of Non-Small Cell Lung Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

AL008 Enhances Myeloid Antitumor Function by Inhibiting SIRPα Signaling and Activating Fc Receptors. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

In vivo and in vitro activity of an immunoglobulin Fc fragment (Fcab) with engineered Her-2/neu binding sites. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses. [2023]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

A long-acting erythropoietin fused with noncytolytic human Fc for the treatment of anemia. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Fc-engineered antibodies with immune effector functions completely abolished. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The use of Fab-Fc recombinant antibodies for studying the mechanism of triggering the effector activities of immunoglobulins. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Application of the Fc fusion format to generate tag-free bi-specific diabodies. [2010]

11. Switzerland 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Targeting macrophage checkpoint inhibitor SIRPα for anticancer therapy. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity. [2020]