BS006 Injection for Solid Tumors

Recruiting at 1 trial location

Overseen By Yue Su

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Binhui Biopharmaceutical Co., Ltd.

Must not be taking: Anti-herpetic drugs

Disqualifiers: Active CNS metastases, Autoimmune disease, Infections, others

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

Compensation: Varies

Number of Visits: 3

29 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will be a Phase 1, multi-center, open-label, dose escalation followed by the recommended phase 2 dose (RP2D) expansion study to characterize safety, tolerability, biodistribution, virus shedding and preliminary efficacy of intratumoral injection of BS006 in patients with advanced solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are restrictions on certain medications, such as systemic corticosteroids and immunosuppressive drugs, which should not be used within 14 days of starting the study treatment. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment BS006 Injection for solid tumors?

Research shows that the treatment uses a modified virus to help the body's immune system attack cancer cells more effectively. This approach has been shown to improve the ability of immune cells to kill tumor cells in both lab and animal studies, suggesting it could be a promising option for treating solid tumors. ^{1 2 3 4 5}

What safety data exists for BS006 Injection or related treatments?

The safety of treatments targeting PD-1/PD-L1, like BS006 Injection, has been evaluated in various studies. These treatments are generally considered safe, with no evidence of toxicity or autoimmunity in preclinical studies, and they have been widely used in cancer therapy with a good safety profile. ^{6 7 8 9 10}

What makes the BS006 Injection treatment unique for solid tumors?

The BS006 Injection is unique because it uses an oncolytic herpes simplex virus type 2 (oHSV2) that is armed with bispecific antibodies (BsAb) targeting PD-L1/CD3, which not only destroys tumor cells directly but also activates the body's immune cells to attack the tumor, even in cases where the tumor has low PD-L1 expression. This dual action enhances the treatment's effectiveness compared to traditional therapies. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced solid tumors, like melanoma or breast cancer, who can feel or see their tumor, or it's detectable by ultrasound. They should have tried all standard treatments without success, be intolerant to them, or refused them. Their disease must be measurable and they need a life expectancy of at least 12 weeks with good performance status.

Inclusion Criteria

My cancer diagnosis was not based solely on cell samples and I have advanced melanoma or CSCC.

I've either progressed after standard treatment or am ineligible for it, and it's been over 4 weeks or 5 half-lives since my last treatment.

I am fully active or can carry out light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Initial Treatment

Participants receive 3 doses of BS006 intratumorally

6 weeks

3 visits (in-person)

Extended Treatment

Participants may continue to receive BS006 every 2 weeks for up to 12 months

up to 12 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 1 year

Treatment Details

Interventions

• BS006 Injection

Trial Overview The study tests BS006 Injection in patients with advanced solid tumors. It starts by finding the safest dose and then expands to more patients at that dose level. The focus is on safety, how well the body tolerates it, where the drug goes in the body (biodistribution), virus shedding from cells and initial signs of effectiveness.

Participant Groups

Group I: BS006 injection Experimental Treatment 1 Intervention

Subjects will receive BS006 every two weeks, and up to 4mL BS006 will be given. BS006 will be given intratumorally.

Who Is Running the Clinical Trial?

Binhui Biopharmaceutical Co., Ltd.

Lead Sponsor

Trials

15

Recruited

1,100+

Findings from Research

Oncolytic viruses (OVs) combined with bi- and tri-specific T cell engagers (BiTEs and TriTEs) represent a promising new approach in cancer immunotherapy, showing substantial efficacy in various tumor models since 2014.

The integration of T cell receptor mimics into BiTEs is expected to enhance the targeting of intracellular tumor antigens, paving the way for more precise and effective cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bi- and Tri-Specific T Cell Engager-Armed Oncolytic Viruses: Next-Generation Cancer Immunotherapy. Guo, ZS., Lotze, MT., Zhu, Z., et al.[2020]

The newly developed oncolytic herpes simplex virus type 2 (oHSV2) armed with bispecific antibodies (BsAb) targeting PD-L1/CD3 demonstrated improved oncolytic potency in both laboratory and animal models, effectively killing tumor cells and activating immune responses.

This approach not only enhances the direct destruction of tumors but also transforms 'cold tumors' with low PD-L1 expression into 'hot tumors' with high PD-L1 expression, making them more susceptible to immune attack and improving the overall efficacy of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibody Expressed by an Oncolytic Herpes Simplex Virus Type 2 Can Transform Heterologous T Cells Into Uniform Tumor Killer Cells. Jin, J., Wang, R., Yang, J., et al.[2023]

The newly developed oncolytic herpes simplex virus, oHSV2-PD-L1/CD3-BsAb, has shown promising anti-tumor efficacy and is designed to selectively target and kill cancer cells while sparing normal tissues.

Comprehensive preclinical safety evaluations in cynomolgus monkeys confirmed that oHSV2-PD-L1/CD3-BsAb is safe, leading to its approval by the FDA to begin Phase I clinical trials in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety assessment of an oncolytic herpes simplex virus type 2 expressed PD-L1/CD3 bispecific antibody. Wang, Y., Wang, R., Hu, H., et al.[2023]

In a phase I trial involving 41 patients with recurrent glioblastoma (rGBM), the oncolytic herpes virus CAN-3110 was safely administered without dose-limiting toxicities, showing potential for preferential tumor replication due to its unique genetic modifications.

Patients with pre-existing HSV1 antibodies experienced improved survival and tumor response, suggesting that CAN-3110 can enhance immune responses against tumors even in challenging microenvironments, providing a promising avenue for treating cancers resistant to traditional immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Ling, AL., Solomon, IH., Landivar, AM., et al.[2023]

The novel bispecific antibody YG-003D3 effectively targets both PD-1 and LAG-3 immune checkpoints, enhancing immune cell activation and demonstrating superior anti-tumor effects compared to single or combined therapies in vitro and in a mouse model.

In humanized mouse models, YG-003D3 not only showed strong anti-tumor activity but also significantly increased the presence of key immune cells (CD45+, CD3+, CD8+ T cells) in the tumor microenvironment, indicating its potential as a promising candidate for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy. Shi, N., Zhou, Y., Liu, Y., et al.[2023]

The PD-1 B-cell epitope vaccine (PD1-Vaxx) has been developed as a potential alternative to nivolumab therapy and has received ethics approval for a Phase 1 clinical trial in Australia.

The vaccine has also gained Investigational New Drug approval from the US FDA for testing in non-small cell lung cancer (NSCLC), and it shows promising synergy when combined with an HER-2 targeted vaccine (B-Vaxx).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First prototype checkpoint inhibitor B-cell epitope vaccine (PD1-Vaxx) en route to human Phase 1 clinical trial in Australia and USA: exploiting future novel synergistic vaccine combinations. Guo, L., Kaumaya, PTP.[2022]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

The novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

JTX-4014, a new PD-1 targeting antibody, was well tolerated in a trial with 18 patients and did not show new safety concerns compared to existing PD-1 inhibitors, establishing a recommended dose of 500 mg every 3 weeks or 1000 mg every 6 weeks.

The treatment demonstrated clinical activity with a 16.7% overall response rate and a 44.4% disease control rate, particularly in patients with PD-L1 positive tumors, suggesting potential for further development in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors. Papadopoulos, KP., Lakhani, N., Falchook, GS., et al.[2021]

Anti-PD-1/PD-L1 antibodies, evaluated in 51 trials with 6,800 patients, showed overall response rates of 29% for melanoma and 21% for both non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), indicating their efficacy in treating advanced or refractory cancers.

These antibodies, particularly Nivolumab and Pembrolizumab, not only increased response rates significantly but also reduced the risk of death and adverse effects compared to other therapies, highlighting their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis. Zhang, T., Xie, J., Arai, S., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Bi- and Tri-Specific T Cell Engager-Armed Oncolytic Viruses: Next-Generation Cancer Immunotherapy. [2020]

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

Bispecific Antibody Expressed by an Oncolytic Herpes Simplex Virus Type 2 Can Transform Heterologous T Cells Into Uniform Tumor Killer Cells. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Preclinical safety assessment of an oncolytic herpes simplex virus type 2 expressed PD-L1/CD3 bispecific antibody. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Clinical trial links oncolytic immunoactivation to survival in glioblastoma. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

First prototype checkpoint inhibitor B-cell epitope vaccine (PD1-Vaxx) en route to human Phase 1 clinical trial in Australia and USA: exploiting future novel synergistic vaccine combinations. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. [2022]

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

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors. [2021]

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

The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis. [2022]