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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for kidney cancer, using a dendritic cell vaccine (Autologous alpha-DC1/TBVA vaccine) and an oral medication called cabozantinib. The main goal is to assess how effectively this combination triggers an immune response against the cancer and to evaluate its safety. Researchers seek participants with a specific type of kidney cancer called clear cell renal cell carcinoma, who have been recently diagnosed and are planning surgery. Individuals with this condition who test positive for a particular immune marker (HLA-A2) might be suitable for the treatment group in this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the dendritic cell vaccine, a key part of this study, has been used in other cancer trials. Early results suggest it might trigger an immune response, which is promising. However, detailed safety information from large groups remains limited.

Cabozantinib has been studied in many patients with kidney cancer and other conditions. Research indicates that cabozantinib can slow disease progression, and many patients tolerate it well. Common side effects include fatigue, diarrhea, and appetite loss, but these can often be managed.

This trial is in a middle stage, meaning the treatments have been tested in humans before, but more information is still being collected to fully understand their safety. Prospective participants should discuss with their doctor how these treatments might affect them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the dendritic cell vaccine and cabozantinib for kidney cancer because it offers a fresh approach to treating this condition. Unlike standard treatments like surgery or targeted therapies, the dendritic cell vaccine is designed to stimulate the patient's immune system to recognize and fight the cancer cells more effectively. Cabozantinib, on the other hand, inhibits specific pathways that promote tumor growth and spread. This dual approach not only targets the cancer directly but also enhances the body's natural defenses, potentially leading to better outcomes for patients with clear cell renal cell carcinoma.

What evidence suggests that the combination of dendritic cell vaccine and cabozantinib could be an effective treatment for kidney cancer?

Research has shown that dendritic cell vaccines, such as the autologous alpha-DC1/TBVA vaccine, can enhance the immune system's ability to combat cancer cells. These vaccines are most effective when patients exhibit a strong immune response. In this trial, participants who are HLA-A2 positive will receive the autologous alpha-DC1/TBVA vaccine. Studies on cabozantinib, a medication for kidney cancer, have demonstrated its ability to slow the disease or reduce the risk of death by 34%. It also achieves a higher success rate in shrinking tumors, with a 33% response rate compared to some other treatments. This trial examines both treatments to determine if they can improve outcomes for kidney cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Jodi Maranchie, MD

Principal Investigator

UPMC Department of Urology

Walter Storkus, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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