PBA-0405 for Cancer

No longer recruiting at 3 trial locations

Overseen By Presage Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Pure Biologics S.A.

Must not be taking: Chemotherapy, Immunosuppressants, Glucocorticoids, others

Disqualifiers: Uncontrolled illness, HIV/AIDS, Hepatitis, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new treatment, PBA-0405 (a CD16-based ROR1-targeted NK Cell Engager), affects cancer cells when injected directly into tumors. Researchers administer the treatment in tiny doses to observe its biological impact on the tumor environment. It targets individuals with specific types of head and neck cancer, soft tissue sarcoma, or triple-negative breast cancer who are planning surgery. Participants should have a tumor that is easily accessible and scheduled for surgical removal. As an Early 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 innovative therapy.

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 prior data suggests that the CIVO device is safe for delivering PBA-0405?

Earlier studies tested PBA-0405, a new cancer treatment, for safety. In tests on acute myeloid leukemia (AML), PBA-0405 helped patients live longer without major side effects, indicating that the treatment was generally well-tolerated. However, as PBA-0405 remains in the early stages of human testing, further research is necessary to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which typically involve systemic chemotherapy or radiation, PBA-0405 is administered directly into the tumor using a unique method called the CIVO device. This device allows for precise delivery of subtherapeutic microdoses directly into the tumor tissue, potentially minimizing side effects associated with traditional treatments. Researchers are excited about this approach because it targets the tumor more directly, which could enhance effectiveness and reduce damage to surrounding healthy tissues. The innovative delivery method might also allow for quicker assessment of how the tumor responds to the treatment, offering valuable insights for future cancer therapies.

What evidence suggests that PBA-0405 might be an effective treatment for cancer?

Research shows that PBA-0405, the investigational treatment in this trial, could be a promising cancer therapy. This treatment uses natural killer (NK) cells, a type of immune cell, to target ROR1, a protein often found on cancer cells. Studies suggest that NK cells can destroy cancer cells while sparing normal cells. In tests with acute myeloid leukemia, these NK cells improved survival rates. Early tests also indicate that PBA-0405 works without causing serious side effects, suggesting it might be safe for humans. Although still in early stages, PBA-0405 offers hope for effectively fighting cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

John Weinberg

Principal Investigator

Pure Biologics

Are You a Good Fit for This Trial?

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

My cancer diagnosis is HNSCC, STS, or TNBC and my tumor is scheduled for surgery.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Microdose Administration

Intratumoral microdose administration of PBA-0405 using the CIVO device

1-2 days

1 visit (in-person)

Surgical Intervention and Assessment

Surgical resection of the tumor and assessment of tumor response via histological staining

1-2 days after microdose injection

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

What Are the Treatments Tested in This Trial?

Interventions

• PBA-0405

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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 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]

Citations

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cancer.gov

cancer.gov/publications/dictionaries/cancer-drug/def/cd16-based-ror1-targeted-nk-cell-engager-pba-0405

CD16-based ROR1-targeted NK cell engager PBA-0405

Upon administration, CD16-based ROR1-targeted NK cell engager PBA-0405 targets and binds to ROR1 expressed on tumor cells and simultaneously binds to the ...

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withpower.com

withpower.com/trial/early-phase-1-breast-cancer-triple-negative-breast-cancer-tnbc-2-2024-2cbff

PBA-0405 for Cancer · Info for Participants

Specifically, CD16+ NK-92 cells have shown improved survival in AML models without significant toxicity. Additionally, a trifunctional NK cell engager targeting ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11794116/

Natural killer cell engagers for cancer immunotherapy - PMC

This review article explores the rapidly evolving field of bi-, tri-, and multi-specific NK cell engagers (NKCEs), highlighting their potential as a cutting- ...

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purebiologics.com

purebiologics.com/project/pb004-purebike/

PB004 - Harnessing the power of antibodies and aptamers

The aim of the PB004 project is to develop an anti-cancer therapeutic based on an anti-ROR1 antibody, with significantly improved therapeutic properties ...

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sitcancer.org

sitcancer.org/2025/abstracts/titles-and-publications?SITC%202025%20Abstracts%5BhitsPerPage%5D=100&SITC%202025%20Abstracts%5Bpage%5D=5

Titles and Publications - SITC 2025

Targeting CXCR1 Overcomes NK Cell Exhaustion in Hepatocellular Carcinoma. Presenting Author Yan Li – The First Affliated Hospital of USTC. Authors ...

6.

nature.com

nature.com/articles/s41423-024-01145-x

Development of NK cell-based cancer immunotherapies ...

This review focuses on surface receptor engineering in NK cell therapy and discusses its impact, challenges, and future directions.

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innate-pharma.com

innate-pharma.com/sites/default/files/Sanofi%20FPI%20PR%20ENG.pdf

Innate Pharma Announces Worldwide Exclusive License with ...

CANCERS. • Partner Sanofi advances IPH6101/ SAR443579, a novel NKp46/CD16-based,. CD123 targeted NK cell engager, to first-in-human clinical trial in relapsed ...