Intratumoral VAX014 for Cancer

Recruiting at 8 trial locations

Overseen By Kate Peters, BA

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

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called VAX014 for people with advanced solid tumors, which are cancers without a liquid component. Researchers inject VAX014 directly into the tumor, either alone or with other cancer drugs, to determine its ability to kill cancer cells. Ideal participants have cancer that has returned or not responded to standard treatments and possess tumors suitable for direct injection. As a Phase 1 trial, this research focuses on understanding how VAX014 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that VAX014, when used alone, demonstrates promising safety results in patients with advanced solid tumors. Studies have found it to be generally well-tolerated, even in patients who have undergone multiple prior treatments. Early signs indicate that it can trigger an immune response, suggesting potential effectiveness.

When combined with either nivolumab or pembrolizumab, VAX014 has shown similar safety results. These combinations are being tested to determine if they can enhance the body's ability to fight tumors. Both nivolumab and pembrolizumab have approval for certain types of cancer, offering some reassurance about their safety.

Overall, current findings suggest that VAX014, whether used alone or with nivolumab or pembrolizumab, shows good safety in trials so far. However, it is important to note that this research is still in the early stages, and ongoing studies will provide more detailed safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VAX014 because it uses recombinant bacterial minicells (rBMCs) for intratumoral injections, offering a unique approach to treating solid tumors that are resistant to standard treatments. Unlike conventional therapies like chemotherapy or radiation, which can affect the whole body, VAX014 is directly injected into the tumor, potentially reducing side effects and enhancing effectiveness. Additionally, when combined with immune checkpoint inhibitors like nivolumab or pembrolizumab, VAX014 may boost the immune system's ability to recognize and attack cancer cells, offering a promising new strategy for tough-to-treat cancers.

What evidence suggests that VAX014 could be an effective treatment for advanced solid tumors?

Research has shown that VAX014, when injected directly into tumors, can help the body’s immune system fight cancer cells. This trial includes a treatment arm where participants will receive VAX014 alone, which increases certain white blood cells, called tumor-infiltrating lymphocytes (TILs), that attack cancer. Studies also indicate that VAX014 activates specific processes, known as STING and RIG-I, which are important for fighting tumors. Another arm of this trial will test VAX014 in combination with drugs like nivolumab and pembrolizumab. Early evidence suggests that this combination could strengthen the overall immune response against solid tumors. Although still in early testing, these findings highlight the potential of VAX014 to treat advanced cancers. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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

Informed consent

Measurable disease by RECIST v1.1

Adequate hematologic function defined as: Absolute neutrophil count >1,500/uL, Platelet count >100,000/uL

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: VAX014 in Combination with Either Nivolumab or Pembrolizumab (Dose Expansion) Experimental Treatment 2 Interventions

Dose expansion of VAX014 \[recombinant bacterial minicells (rBMCs)\] intratumoral injections in combination with Investigator's choice of nivolumb or pembrolizumab 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, with the assistance of ultrasound, or interventional radiology.

Group II: VAX014 (Dose Escalation) 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.

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05901285

NCT05901285 | Phase 1 Study of Intratumoral ... The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for intratumoral injections (VAX014) as a single agent as ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10254596/

Intralesional administration of VAX014 facilitates in situ ... Intratumoral administration of VAX014 increases TILs, upregulates multiple immune gene networks, and results in systemic tumor-specific cellular ...

3. aacrjournals.org aacrjournals.org/mct/article/24/4/587/754290/VAX014-Activates-Tumor-Intrinsic-STING-and-RIG-I

VAX014 Activates Tumor-Intrinsic STING and RIG-I to Promote ... Analysis of human solid tumor datasets demonstrated STING and RIG-I co-expression is prevalent in solid tumors and associates with clinical benefit in many ...

4. onclive.com onclive.com/view/vax014-demonstrates-safety-early-signs-of-immune-mediated-activity-in-advanced-solid-tumors

VAX014 Demonstrates Safety, Early Signs of Immune- ... VAX014 showed promising antitumor activity and tolerability in heavily pretreated patients with advanced solid tumors during the phase 1 trial.

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/436555

Phase 1 Study of Intratumoral Administration of VAX014 ... The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for intratumoral injections (VAX014) as a ...

6. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A765

667 Phase 1 study of intratumoral administration ... VAX014 is being evaluated for intratumoral treatment of advanced solid tumors in a two-part multi-center Phase 1 dose escalation (Phase 1a) and dose expansion ...

7. vaxiion.com vaxiion.com/vax014-description

VAX014 description - Vaxiion Therapeutics VAX014 is a first-in-class tumor targeted oncolytic immunotherapy based on recombinant bacterial minicells (rBMCs). VAX014 contains four major components.