Dendritic Cell Vaccine + Cabozantinib for Kidney Cancer

Overseen By Morgan Pokora, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jodi Maranchie

Must not be taking: Immunosuppressants, Steroids, Anticoagulants, others

Disqualifiers: Metastatic disease, Hepatitis, Hypertension, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

42 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently on certain treatments like systemic immunosuppressive agents, some anticoagulants, or have had recent cancer therapies. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Dendritic Cell Vaccine + Cabozantinib for Kidney Cancer?

Research shows that dendritic cell vaccines, when combined with other treatments, have shown promise in treating kidney cancer. For example, a study found that a dendritic cell vaccine combined with another drug, sunitinib, is being tested for effectiveness in kidney cancer patients. Additionally, combining dendritic cell vaccines with other therapies has enhanced antitumor effects in animal studies. ^{1 2 3 4 5}

Is the dendritic cell vaccine safe for humans?

The dendritic cell vaccine has been studied in various forms for kidney cancer and has shown potential as a safe treatment in mouse models, but specific human safety data for this combination with Cabozantinib is not detailed in the provided research. ^{2 3 4 6 7}

How is the Dendritic Cell Vaccine + Cabozantinib treatment for kidney cancer different from other treatments?

This treatment is unique because it combines a dendritic cell vaccine, which helps the immune system recognize and attack cancer cells, with Cabozantinib, a drug that blocks signals that help cancer grow. This combination aims to enhance the body's immune response against kidney cancer, offering a novel approach compared to standard treatments. ^{2 3 4 6 8}

What is the purpose of this trial?

The purpose of this study is to estimate the probability of immune response for the combination treatment of dendritic cell vaccine with oral cabozantinib and characterize the safety profile of interventional therapy.

Research Team

Jodi Maranchie, MD

Principal Investigator

UPMC Department of Urology

Walter Storkus, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults with clear cell renal cancer that hasn't spread and can be surgically removed. Participants must understand the study, agree to use contraception, not be pregnant, have good organ function, an ECOG status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and must have HLA-A2+ if receiving the vaccine.

Inclusion Criteria

I am not pregnant and can become pregnant.

I am 18 or older and can care for myself with minimal assistance.

My recent tests show my organs and bone marrow are working well.

Exclusion Criteria

My cancer has spread to other parts of my body.

I am not on strong immune system suppressing drugs, except for low-dose steroids for hormone issues.

I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant autologous Tumor Blood Vessel Antigen (TBVA)-Dendritic Cell Vaccine intradermally every 2 weeks for 2 doses, along with oral cabozantinib 20 mg daily for 10 days prior to surgery

4 weeks

2 visits (in-person) for vaccine administration

Surgery

Participants undergo surgical resection of the renal tumor

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of immune response and vascular normalization

48 months

Treatment Details

Interventions

• Autologous alpha-DC1/TBVA vaccine
• Cabozantinib

Trial Overview The study tests a combination treatment: a personalized dendritic cell vaccine alongside oral cabozantinib medication. The goal is to see how well patients' immune systems respond to this combo and what side effects might occur.

Participant Groups

Group I: HLA-A2 postive Experimental Treatment 2 Interventions

The study will include 21 participants over the 18 years of age with newly diagnosed, clinically localized clear cell renal cell carcinoma, planned for surgical resection with curative intent. Participants receiving vaccine much be HLA-A2 positive.

Group II: HLA-A2 negative Active Control 1 Intervention

Up to 21 additional participants who screen as HLA-A2 negative will be enrolled as non-treatment controls. These participants will not be required to undergo blood collection or study procedures

Autologous alpha-DC1/TBVA vaccine is already approved in European Union, United States for the following indications:

Approved in European Union as Autologous dendritic cell vaccine - Amphera for:

• Pancreatic cancer
• Mesothelioma

Approved in United States as Autologous dendritic cell vaccine - Amphera for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

Jodi Maranchie

Lead Sponsor

Trials

2

Recruited

80+

Findings from Research

The study involved 82 patients with advanced renal cell carcinoma, showing that dendritic cells (DCs) sensitized with autologous tumor cell lysate significantly enhanced the immune response, particularly increasing the proliferation of cytokine-induced killer (CIK) cells and the release of IL-12.

Patients receiving the Ag-DC-CIK vaccine had better clinical responses compared to those receiving CIK cell therapy alone, with no severe adverse effects reported, indicating a promising and safe immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma]. Wang, H., Feng, F., Zhu, M., et al.[2021]

AGS-003, an autologous dendritic cell vaccine, is currently in Phase III clinical trials combined with sunitinib for treating patients with intermediate- and poor-risk clear cell metastatic renal cell carcinoma (ccmRCC).

If successful, this combination treatment could significantly improve survival rates with minimal toxicity, potentially changing the standard care approach for ccmRCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized immunotherapy ( AGS-003 ) when combined with sunitinib for the treatment of metastatic renal cell carcinoma. Figlin, RA.[2022]

In a study involving Balb/c mice with renal cell carcinoma, combining a dendritic cell-based vaccine with anti-CD69 antibody significantly reduced tumor volume compared to untreated mice or either treatment alone.

The enhanced effectiveness of this combination therapy is linked to increased T-cell proliferation and activity, suggesting a stronger immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody enhances antitumor efficacy in renal cell carcinoma-bearing mice. Wei, SM., Pan, HL., Wang, L., et al.[2018]

In a study involving 18 patients with metastatic renal cell carcinoma, a combination of dendritic cell vaccines with IL-2 and IFN-alpha 2a resulted in a 50% overall objective clinical response rate, including three complete responses.

The treatment showed promising immunologic changes, with the level of circulating CD4(+) T regulatory cells correlating strongly with patient outcomes, suggesting that this combination therapy may effectively modulate immune responses in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients. Schwaab, T., Schwarzer, A., Wolf, B., et al.[2021]

In a pilot study involving two male patients with metastatic renal cell carcinoma (RCC), a combination of sunitinib, nephrectomy, and a dendritic cell vaccine resulted in stable disease for 9 to 10 months, indicating potential efficacy of this triple therapy approach.

The treatment strategy leverages the immune response from the dendritic cell vaccine alongside the antiangiogenic effects of sunitinib and the benefits of cytoreductive nephrectomy, suggesting a promising new option for managing treatment-resistant metastatic RCC, though further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early experience with targeted therapy and dendritic cell vaccine in metastatic renal cell carcinoma after nephrectomy. Dall'Oglio, MF., Sousa-Canavez, JM., Tanno, FY., et al.[2020]

The dendritic cell vaccine DC-Ad-GM·CAIX significantly delayed tumor development and reduced tumor volume in a mouse model of renal cell carcinoma, demonstrating its potential as a safe and effective immunotherapy, with some mice remaining tumor-free for over a year.

In treatment models, the vaccine also inhibited tumor growth by 60% without causing any organ toxicity, indicating its safety and efficacy, and highlighting the importance of hCAIX protein expression for the vaccine's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell-based immunotherapy in prevention and treatment of renal cell carcinoma: efficacy, safety, and activity of Ad-GM·CAIX in immunocompetent mouse models. Birkhäuser, FD., Koya, RC., Neufeld, C., et al.[2022]

The study involved 15 patients with metastatic renal cell carcinoma (mRCC) who received an irradiated autologous tumor cell vaccine combined with CpG oligodeoxynucleotide and GM-CSF, showing that the treatment was well tolerated and safe.

The treatment led to objective clinical responses in three patients, including one long-term complete response, and demonstrated significant immune activation, suggesting potential benefits when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial. Koster, BD., Santegoets, SJAM., Harting, J., et al.[2020]

Dendritic cell (DC) vaccines for renal cell carcinoma have shown safety in clinical trials, but their effectiveness has been limited, highlighting the need for improved strategies.

Enhancing DC vaccines with mature dendritic cells, better antigen sources, and the secretion of IL-12 could boost their ability to stimulate the immune system and improve treatment outcomes, especially when combined with therapies that address systemic immune suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccine strategies for renal cell carcinoma. Schendel, DJ.[2019]

References

1. China pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma]. [2021]

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

Personalized immunotherapy ( AGS-003 ) when combined with sunitinib for the treatment of metastatic renal cell carcinoma. [2022]

3. Turkey pubmed.ncbi.nlm.nih.gov

Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody enhances antitumor efficacy in renal cell carcinoma-bearing mice. [2018]

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

Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients. [2021]

5. Brazil pubmed.ncbi.nlm.nih.gov

Early experience with targeted therapy and dendritic cell vaccine in metastatic renal cell carcinoma after nephrectomy. [2020]

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

Dendritic cell-based immunotherapy in prevention and treatment of renal cell carcinoma: efficacy, safety, and activity of Ad-GM·CAIX in immunocompetent mouse models. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccine strategies for renal cell carcinoma. [2019]