Oncolytic Virus + CAR T-Cell Therapy for Solid Cancers

(VISTA Trial)

Overseen By Dustin McFadden

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, Immunotherapy, Cytotoxic agents

Disqualifiers: Autoimmune, Immunodeficiency, Other malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with HER2-positive solid cancers, such as certain breast and lung cancers. It combines HER2-specific CAR T cells with an oncolytic virus (CAdVEC) that targets tumors. The trial aims to determine if this combination is safe and more effective than using each treatment separately. Suitable candidates have HER2-positive cancers unresponsive to standard treatments and a tumor that can be directly injected with the virus. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on continuous high-dose corticosteroids or other active treatments that could interfere with the study. 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 has shown that oncolytic viruses like CAdVEC are generally well-tolerated in treating solid cancers. In one study, patients with advanced cancers responded well to this treatment. Oncolytic viruses are designed to infect and destroy cancer cells and may also help the immune system fight tumors.

For HER2-specific CAR T cells, research indicates they have demonstrated activity against tumors in patients. In a study involving patients with an aggressive type of brain cancer, these CAR T cells were found to be safe, with no serious side effects reported.

Both treatments in this trial, CAdVEC and HER2-specific CAR T cells, have shown promise in earlier studies without major safety concerns. However, this trial is in its early phase, focusing on understanding safety in humans. More research is needed to confirm the safety and effectiveness of these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Oncolytic Virus (CAdVEC) and HER2-Specific Autologous CAR T-Cell Therapy because it represents a novel approach to tackling solid tumors. Unlike traditional treatments like chemotherapy and radiation, which often have broad and harsh effects, CAdVEC selectively infects and destroys cancer cells while sparing healthy ones. Additionally, the CAR T-cell component specifically targets the HER2 protein, which is overexpressed in many cancers, enhancing precision and efficacy. This dual strategy not only aims to improve effectiveness but also to reduce side effects, offering new hope for patients with solid cancers.

What evidence suggests that this trial's treatments could be effective for HER2 positive cancer?

Research has shown that CAdVEC, a type of virus that targets cancer, can effectively destroy cancer cells by infecting them and prompting the immune system to attack the tumor. Studies have also found that these viruses can enhance the body's immune response against cancer. In one study, a combination of this virus and another treatment resulted in a cure rate of 66.7%, which is promising compared to using other treatments alone.

In this trial, some participants will receive CAdVEC alone, while others will receive a combination of CAdVEC and HER2-specific CAR T cells. HER2-specific CAR T cells are specially designed immune cells that aim to find and kill cancer cells with the HER2 protein. Although these cells have been effective in some cases, challenges remain in making them grow and persist in the body, which is crucial for their success. Combining these two treatments might enhance their effectiveness, as each supports the other in fighting the tumor. ^{2 4 5 6 7}

Who Is on the Research Team?

Shalini Makawita, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Adults with advanced HER2 positive solid tumors, including breast, lung, and other cancers listed. They must have tried standard treatments without success or have no effective options left. Participants need to be in relatively good health (ECOG ≤ 2), not pregnant or breastfeeding, willing to use contraception, and have a tumor that can safely receive injections.

Inclusion Criteria

I have a tumor that can be injected directly.

I can take care of myself but cannot do heavy physical work.

I had HER2 targeted therapy over 4 weeks ago.

Exclusion Criteria

I have been diagnosed with HIV or another immune system disorder.

Pregnant or breastfeeding females.

I haven't had any cancer except for some skin, thyroid, prostate, or cervical cancers in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intratumoral injection of CAdVEC followed by HER2-specific CAR T cells

6 weeks

Multiple visits for injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular visits for blood samples and monitoring

Long-term follow-up

Participants are monitored for long-term safety and survival outcomes

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CAdVEC
• HER2-Specific Autologous CAR VST

Trial Overview The trial is testing the combination of CAdVEC (an oncolytic virus injected into the tumor) with HER2-specific CAR T cells (immune cells designed to target cancer). The goal is to see if this combo is more effective than individual treatments by activating the immune system against cancer.

How Is the Trial Designed?

Group I: Treatment Phase Experimental Treatment 1 Intervention

Five dose levels will be evaluated using the BOIN design. Cohorts of size 3 will be enrolled at each dose level until 9 evaluable patients have been studied at a single dose. Each patient will receive an intratumoral injection of CAdVEC alone on Day 1 or combined with an injection of HER2.CAR.T cells on Day 4, according to the following dose levels: Dose Level 1 CAdVEC = 5.00E+9 HER2 specific CAR-T cells = 0 Dose Level 2 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 0 Dose Level 3 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+06 Dose Level 4 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+07 Dose Level 5 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+08

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

HER2 is commonly expressed in osteosarcoma but at low levels, making traditional HER2 monoclonal antibody treatments ineffective; however, genetically modified T cells with HER2-specific chimeric antigen receptors (CARs) can effectively target these tumors.

In mouse models, the adoptive transfer of HER2-specific T cells led to significant regression of established osteosarcoma tumors, demonstrating the potential of CAR T-cell therapy in treating cancers with low antigen expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Ahmed, N., Salsman, VS., Yvon, E., et al.[2021]

CAR T-cell therapy has shown great success in treating advanced hematological malignancies, but it faces significant challenges when targeting solid tumors, including difficulties in cell trafficking, expansion, and persistence.

Combining CAR T-cells with oncolytic virotherapy presents a promising strategy to enhance treatment outcomes for patients with advanced solid tumors, potentially overcoming some of the limitations faced by CAR T-cells alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic combination of oncolytic virotherapy with CAR T-cell therapy. Ajina, A., Maher, J.[2021]

VHH-based CAR T cells targeting the checkpoint inhibitor PD-L1 in the tumor microenvironment showed a reduction in tumor growth and improved survival in animal models, highlighting their potential efficacy against solid tumors.

Additionally, CAR T cells targeting the EIIIB+ fibronectin splice variant, present in various tumor types and neovasculature, were also effective in delaying tumor growth, demonstrating the versatility of this approach in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Xie, YJ., Dougan, M., Jailkhani, N., et al.[2020]

Talimogene laherparepvec (T-VEC) has been approved for treating inoperable melanoma, marking a significant advancement in oncolytic virotherapy as a cancer treatment option.

Combining oncolytic virotherapy with CAR T-cell therapy may improve treatment outcomes for solid tumors by enhancing T-cell movement into tumors and overcoming local immunosuppression, which has been a challenge for CAR T-cell effectiveness in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for combined use of oncolytic viruses and CAR T-cells. Ajina, A., Maher, J.[2021]

HER2-specific T cells can effectively recognize and kill HER2-positive medulloblastoma cells, showing significant T-cell activation and proliferation in response to these tumors.

In vivo studies demonstrated that transferring HER2-specific T cells led to sustained regression of established medulloblastomas, suggesting that this approach could be a promising immunotherapy for treating this type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Ahmed, N., Ratnayake, M., Savoldo, B., et al.[2014]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

CAR T-cell therapy has shown great promise in treating blood cancers but faces significant challenges when applied to solid tumors, such as breast cancer, due to issues like poor T cell trafficking and an immunosuppressive tumor environment.

Current research is focused on developing strategies to improve the effectiveness of CAR T-cells in solid tumors, aiming to overcome the limitations that have hindered their success in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. Rahimmanesh, I., Khanahmad, H.[2021]

The chA21-4-1BBz CAR T cells demonstrated a strong ability to target and kill HER2 overexpressing gastric cancer cells in laboratory tests, showing a Th1 skewed cytokine response that correlates with HER2 levels on tumor cells.

In animal models, these CAR T cells significantly reduced tumor size and improved survival in mice with HER2 overexpressing tumors, while not affecting tumors with low HER2 expression, indicating a targeted and potentially safer treatment approach for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models. Han, Y., Liu, C., Li, G., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12282134/

Efficacy of oncolytic virus in the treatment of intermediate-to ... In conclusion, this meta-analysis reveals that OVs demonstrate a significant therapeutic effect in the treatment of solid tumors. Specifically, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0168365925004420

Advancing systemic delivery and immune amplification Oncolytic viruses (OVs) selectively infect and destroy tumor cells, induce immunogenic cell death (ICD) and stimulate antitumor immune responses ...

3. link.springer.com link.springer.com/article/10.1007/s40259-025-00743-z

Oncolytic Virotherapy in Solid Tumors: A Current Review The cure rate of the combination therapy was 66.7%, compared to 21.4% for radiation alone and 13.3% for virus alone [192]. A single-center, dose ...

4. clinicaltrials.gov clinicaltrials.gov/show/NCT06910657

NCT06910657 | IDOV-Immune for Advanced Solid Tumors Oncolytic viruses have the potential for destroying cancer cells and activating anti-tumor immune responses. IDOV-Immune's multi-pronged design - combining ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00294-9/fulltext

Comparative safety and efficacy of oncolytic virotherapy for ... Adults demonstrated higher objective response rate (14.13%, 11.07–17.44, I2 = 86.10%) than children (0.50%, 0.04–5.16, I2 = 7.80%; p = 0.00020, adjusted p = ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8799180/

The efficacy and safety of oncolytic viruses in the treatment ... OVs are effective and well tolerated for the treatment of intermediate to advanced solid cancer and represent a promising therapeutic approach for solid cancers ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12567567/

Efficacy, Safety and Predictive Biomarkers of Oncolytic Virus ... Talimogene laherparepvec (T-VEC), a modified herpes simplex virus, has been approved by the U.S. FDA for advanced melanoma, paving the way for ...