Intratumoral VAX014 for Cancer

Recruiting at 7 trial locations

Overseen By Gabriela Sanchez, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vaxiion Therapeutics

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Severe infection, Hepatitis, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for intratumoral injections (VAX014) in patients with advanced solid tumors. VAX014 is a targeted oncolytic agent designed to kill tumor cells following intratumoral injection into advanced solid tumors.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 21 days from your last anticancer therapy before starting the trial.

What data supports the effectiveness of the treatment VAX014 for cancer?

Research shows that VAX014, when injected directly into tumors, can help the immune system attack cancer cells more effectively, especially when combined with other immune therapies. In studies with colorectal cancer, VAX014 reduced tumor size and number, suggesting it might be a promising treatment for certain cancers. ^{1 2 3 4 5}

How is the treatment VAX014 different from other cancer treatments?

VAX014 is unique because it is a non-viral oncolytic agent that is directly injected into tumors, which helps to stimulate the immune system locally and can enhance the effectiveness of systemic immune checkpoint inhibitors. This approach is particularly promising for 'immune cold' tumors that typically do not respond well to traditional immune therapies. ^{2 6 7 8 9}

Eligibility Criteria

This trial is for adults with advanced solid tumors that have stopped responding to standard treatments. Participants must have a tumor between 1 and 10 cm in size that can be injected directly or with ultrasound guidance, and they should not be candidates for surgery or systemic treatment as per the investigator's assessment.

Inclusion Criteria

I am 18 years old or older.

Measurable disease by RECIST v1.1

Informed consent

Exclusion Criteria

I am on a daily dose of more than 10 mg of prednisone or its equivalent.

I have an active Hepatitis B or C infection.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects receive weekly intratumoral injections of VAX014 for dose escalation to determine the maximum tolerated dose (MTD).

8 weeks

8 visits (in-person)

Dose Expansion

Subjects receive intratumoral injections at the Recommended Phase 2 Dose (RP2D) determined at the end of the Dose Escalation Phase.

Up to 20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

Treatment Details

Interventions

• VAX014

Trial Overview The study is testing VAX014, an experimental cancer therapy given by injection directly into the tumor. The goal is to see if it's safe, tolerable, and effective at killing cancer cells in patients with advanced solid tumors.

Participant Groups

Group I: VAX014 Experimental Treatment 1 Intervention

Dose escalation of VAX014 \[recombinant bacterial minicells (rBMCs)\] intratumoral injections alone for subjects with solid tumors relapsed and/or refractory to standard treatment and appropriate for injection of a nodal, subcutaneous, or cutaneous tumor via palpation or with the assistance of ultrasound. In dose expansion, injection may be in metastatic tumors with or without the need for interventional radiology.

VAX014 is already approved in United States for the following indications:

Approved in United States as VAX014 for:

• None approved yet; Phase 1 clinical trial for advanced solid tumors

Who Is Running the Clinical Trial?

Vaxiion Therapeutics

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

Intratumoral therapy for advanced melanoma allows for direct delivery of medications into tumors, potentially increasing local drug concentration and attracting immune cells, which may lead to fewer systemic side effects.

This review highlights that intratumoral therapies can act as in situ vaccines, offering the possibility of controlling disease both locally within the tumor and systemically throughout the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral therapies and in-situ vaccination for melanoma. Huppert, LA., Daud, AI.[2022]

VAX014, a novel oncolytic agent, effectively stimulates local immune responses in injected tumors, leading to increased CD8+ TILs and enhanced antitumor activity, particularly in immune desert tumors.

When combined with systemic immune checkpoint blockade (ICB), VAX014 improves overall survival and boosts systemic antitumor responses, although additional PD-1 blockade is necessary for effective clearance of non-injected tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors. Reil, KA., Tsuji, S., Molina, E., et al.[2023]

Intratumoral delivery of immunotherapy is a promising strategy for treating early-stage solid tumors, as it minimizes severe side effects associated with systemic delivery while enhancing local tumor-specific immunity.

Over 20 ongoing neoadjuvant clinical trials are exploring various intratumoral immune stimulatory agents, indicating a strong interest in optimizing this approach for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral Immunotherapy for Early-stage Solid Tumors. Hong, WX., Haebe, S., Lee, AS., et al.[2021]

The FX@HP nanocomplex, which combines CXCR4 antagonism and paclitaxel, enhances the effectiveness of anti-PD-L1 therapy by promoting T cell infiltration and reducing immunosuppressive cells in the tumor microenvironment.

This innovative approach not only improves the immune response against lung tumors but also decreases tumor fibrosis, suggesting a promising strategy to boost the efficacy of immunotherapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti-PD-L1 immunotherapy. Li, Z., Wang, Y., Shen, Y., et al.[2022]

VAX014, a novel oncolytic bacterial minicell therapy, has shown promise in reducing the size and number of adenomas in colorectal cancer (CRC) models, indicating its potential as a prophylactic treatment.

As a neoadjuvant therapy, VAX014 not only reduced tumor numbers but also enhanced antitumor immune responses and decreased cell proliferation, suggesting it may effectively inhibit adenoma development through both direct oncolytic effects and immune system activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VAX014, an Oncolytic Therapy, Reduces Adenomas and Modifies Colon Microenvironment in Mouse Model of CRC. Grenier, SF., Khan, MW., Reil, KA., et al.[2023]

Talimogene laherparepvec (T-VEC) is the first FDA-approved oncolytic virus therapy for unresectable melanoma, showing a significantly higher durable response rate compared to subcutaneous GM-CSF (16.3% vs. 2.1%).

T-VEC not only targets injected tumors but also induces systemic antitumor responses, as evidenced by responses in both injected and uninjected lesions, especially when combined with immune checkpoint inhibitors, enhancing overall treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral Immunotherapy-Update 2019. Hamid, O., Ismail, R., Puzanov, I.[2021]

Intratumoral treatment with modified vaccinia Ankara (MVA) expressing tumor-associated antigens and the immune-stimulatory ligand 4-1BBL effectively controlled established tumors by reactivating and expanding tumor-specific CD8+ T cells.

This therapy not only induced local tumor elimination but also triggered a systemic immune response that protected against distant untreated tumors, demonstrating its potential for long-lasting immunological memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory. Hinterberger, M., Giessel, R., Fiore, G., et al.[2021]

Direct intratumoral injection of immunotherapeutic agents can lead to local immune activation while reducing systemic toxicity, making it a safer alternative to intravenous administration.

Intratumoral delivery has shown improved efficacy and the potential for abscopal effects, especially when combined with immune checkpoint inhibitors, highlighting its promise in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery routes matter: Safety and efficacy of intratumoral immunotherapy. De Lombaerde, E., De Wever, O., De Geest, BG.[2021]

The use of a CXCR4 antagonist-armed oncolytic vaccinia virus in a metastatic ovarian tumor model significantly reduced tumor load and enhanced the immune response by increasing the infiltration of CD103+ dendritic cells, which are crucial for activating T cells.

Combining this viral therapy with a Wilms tumor antigen peptide-based vaccine led to improved antitumor responses and increased overall survival, demonstrating that enhancing dendritic cell populations can boost the effectiveness of cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recruitment of Intratumoral CD103+ Dendritic Cells by a CXCR4 Antagonist-Armed Virotherapy Enhances Antitumor Immunity. Mistarz, A., Komorowski, MP., Graczyk, MA., et al.[2022]

References

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

Intratumoral therapies and in-situ vaccination for melanoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors. [2023]

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

Intratumoral Immunotherapy for Early-stage Solid Tumors. [2021]

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

Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti-PD-L1 immunotherapy. [2022]

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

VAX014, an Oncolytic Therapy, Reduces Adenomas and Modifies Colon Microenvironment in Mouse Model of CRC. [2023]

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

Intratumoral Immunotherapy-Update 2019. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Delivery routes matter: Safety and efficacy of intratumoral immunotherapy. [2021]

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

Recruitment of Intratumoral CD103+ Dendritic Cells by a CXCR4 Antagonist-Armed Virotherapy Enhances Antitumor Immunity. [2022]