PBA-0405 for Cancer

Recruiting at 3 trial locations

Overseen By Presage Biosciences

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Pure Biologics S.A.

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a multi-center, single arm, open-label, localized pharmacodynamic biomarker Phase 0 trial designed to study the biological effects within the tumor microenvironment of PBA-0405 when administered intratumorally in microdose quantities via the CIVO device.

Do I need to stop my current medications for the trial?

The trial requires stopping certain medications at least 3 weeks before the CIVO injection. These include systemic anti-cancer therapy, immunosuppressive drugs, biological response modifiers for autoimmune disease, systemic glucocorticoids (except for low-dose or specific uses), hematopoietic growth factors, chemotherapy, and local radiotherapy of the target lesion. The protocol does not specify other medications, so consult your doctor for guidance.

What data supports the idea that PBA-0405 for Cancer is an effective treatment?

The available research shows that treatments similar to PBA-0405, which involve engaging natural killer (NK) cells to target cancer cells, have shown promise in treating certain types of cancer. For example, a trifunctional NK cell engager targeting CD123 has demonstrated strong anti-tumor activity in acute myeloid leukemia (AML) models, even outperforming other antibody treatments. Additionally, these NK cell-based therapies have been effective in activating the immune system to fight cancer cells without significant toxicity. While specific data on PBA-0405 is not provided, the success of similar NK cell engager treatments suggests that PBA-0405 could also be effective. ^{1 2 3 4 5}

What safety data is available for the cancer treatment PBA-0405?

The treatment PBA-0405, also known as CD16-based ROR1-targeted NK Cell Engager, is part of a broader category of NK cell engagers that have been studied for their safety and efficacy. The research indicates that NK cell-based therapies, such as those involving CD16+ NK-92 cells, have been tested in preclinical models with minimal toxicity. Specifically, CD16+ NK-92 cells have shown improved survival in AML models without significant toxicity. Additionally, a trifunctional NK cell engager targeting CD123 demonstrated potent antitumor activity in nonhuman primates with no signs of toxicity and low inflammatory cytokine induction. These findings suggest a favorable safety profile for NK cell engager therapies, including PBA-0405, in preclinical studies. ^{1 2 3 5 6}

Is the treatment PBA-0405 a promising treatment for cancer?

Yes, PBA-0405 is a promising treatment for cancer because it uses natural killer (NK) cells to specifically target and destroy cancer cells. This treatment enhances the ability of NK cells to recognize and kill tumor cells, making it a powerful tool in cancer therapy. It also shows potential in improving the effectiveness of existing cancer treatments. ^{1 2 6 7 8}

Research Team

John Weinberg

Principal Investigator

Pure Biologics

Eligibility Criteria

Adults over 18 with certain solid tumors (like oral, breast cancer, or sarcoma) that are planned for surgery can join. They must be able to follow the study plan and agree not to donate eggs or sperm. Women should be postmenopausal, surgically sterile, or use contraception. People with specific types of sarcoma are eligible.

Inclusion Criteria

Ability and willingness to comply with the study's visit and assessment schedule

Ability and willingness to provide written informed consent

I am 18 years old or older.

Exclusion Criteria

I have recently used certain medications or treatments.

I am currently on treatment for an infection.

Uncontrolled intercurrent illness, serious medical or psychiatric illness, or circumstances that could interfere with study procedures

Treatment Details

Interventions

• PBA-0405 (Virus Therapy)

Trial Overview The trial is testing PBA-0405's effects on tumor biology when given in tiny amounts directly into the tumor using a special device called CIVO. It's an early-phase study where everyone gets the same treatment to see how it works inside the tumor.

Participant Groups

Group I: PBA-0405 Experimental Treatment 1 Intervention

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at 1-2 days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline) or subtherapeutic microdoses of PBA-0405, as single agents. Each microdose is simultaneously injected in a columnar fashion through each of 8, or 5, (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.

Who Is Running the Clinical Trial?

Pure Biologics S.A.

Lead Sponsor

Trials

2

Recruited

30+

Presage Biosciences

Industry Sponsor

Trials

10

Recruited

110+

Findings from Research

Multi-specific engagers are a new class of cancer immunotherapies designed to enhance the ability of natural killer (NK) cells to target and destroy tumor cells by engaging specific tumor antigens and NK cell-activating receptors.

These engagers have shown promising results in increasing NK cell cytotoxicity against tumors and can be used alone or in combination with other cancer treatments, making them a versatile option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bi-specific and Tri-specific NK Cell Engagers: The New Avenue of Targeted NK Cell Immunotherapy. Phung, SK., Miller, JS., Felices, M.[2023]

The nanoparticle-based trispecific NK cell engager (nano-TriNKE) effectively targets tumors that overexpress the epidermal growth factor receptor (EGFR), enhancing the recruitment and activation of natural killer (NK) cells to destroy cancer cells.

This platform not only activates NK cells more effectively than free antibodies but also allows for the delivery of chemotherapy (like epirubicin), creating a powerful combination of immunotherapy and chemotherapy for improved cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy. Au, KM., Park, SI., Wang, AZ.[2023]

The engineered trifunctional natural killer cell engager (CD123-NKCE) effectively targets CD123 on acute myeloid leukemia (AML) cells and overcomes resistance caused by CD64 expression, demonstrating potent antitumor activity in vitro and in vivo.

In nonhuman primates, CD123-NKCE showed prolonged effects, depleting CD123+ cells for over 10 days without toxicity or significant inflammatory responses, indicating a promising safety profile for clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123. Gauthier, L., Virone-Oddos, A., Beninga, J., et al.[2023]

A trifunctional natural killer cell engager (NKCE) has been developed that specifically targets and kills CD123+ acute myeloid leukemia (AML) cells, showing promise as a potential treatment for this type of cancer.

This NKCE represents a novel approach to harnessing the body's immune system to fight leukemia, which could lead to more effective therapies for patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Trifunctional Natural Killer Cell Engager Can Target CD123+ Leukemia. [2023]

The study demonstrates that genetically modified CD16+ NK-92 cells, when combined with an anti-CD123 antibody, effectively target and kill leukemic stem cells in acute myeloid leukemia (AML), showing promise for improving treatment outcomes.

In a pre-clinical model, mice treated with irradiated CD16+ NK-92 cells and the anti-CD123 antibody exhibited significantly improved survival compared to those treated with NK-92 cells and a control antibody, indicating the potential efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD16+NK-92 and anti-CD123 monoclonal antibody prolongs survival in primary human acute myeloid leukemia xenografted mice. Williams, BA., Wang, XH., Leyton, JV., et al.[2019]

The second-generation tri-specific killer engager (TriKE) platform enhances natural killer (NK) cell functionality by enabling specific tumor targeting and promoting NK cell expansion, which is crucial for effective immunotherapy.

In preclinical mouse models, the modified TriKE demonstrated improved NK cell activation and tumor control against CD33-expressing targets, suggesting strong potential for clinical application in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cytolytic Activity and Specific IL15 Delivery in a Second-Generation Trispecific Killer Engager. Felices, M., Lenvik, TR., Kodal, B., et al.[2021]

The engineered hnCD16-iNK cells, derived from human induced pluripotent stem cells, show enhanced resistance to activation-induced cleavage and exhibit improved antibody-dependent cellular cytotoxicity (ADCC) against various tumor targets.

In vivo studies demonstrated that hnCD16-iNK cells combined with therapeutic monoclonal antibodies significantly improved tumor regression and survival in models of B-cell lymphoma and ovarian cancer, indicating their potential as an effective off-the-shelf NK cell therapy for hard-to-treat malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity. Zhu, H., Blum, RH., Bjordahl, R., et al.[2023]

The novel CD19-targeting 161519 TriKE molecule effectively activates and expands natural killer (NK) cells, enhancing their ability to kill chronic lymphocytic leukemia (CLL) cells, as demonstrated in both healthy donor and patient samples.

161519 TriKE showed superior in vitro killing of CLL cells compared to the traditional treatment rituximab, highlighting its potential as a promising immunotherapy for patients with refractory CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL. Felices, M., Kodal, B., Hinderlie, P., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Bi-specific and Tri-specific NK Cell Engagers: The New Avenue of Targeted NK Cell Immunotherapy. [2023]

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

Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy. [2023]

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

Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123. [2023]

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

A Trifunctional Natural Killer Cell Engager Can Target CD123+ Leukemia. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

CD16+NK-92 and anti-CD123 monoclonal antibody prolongs survival in primary human acute myeloid leukemia xenografted mice. [2019]

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

Potent Cytolytic Activity and Specific IL15 Delivery in a Second-Generation Trispecific Killer Engager. [2021]

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

Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity. [2023]

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

Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL. [2020]